ORCID Profile
0000-0002-0144-5816
Current Organisation
The University of Newcastle
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Nutrition and Dietetics | Food Processing | Systems Physiology | Nutrition And Dietetics
Publisher: Springer Science and Business Media LLC
Date: 10-05-2011
DOI: 10.1038/IJO.2011.95
Abstract: Angiotensin-converting enzyme (ACE) inhibition can reduce the body weight of mice maintained on a high-fat diet. The current study examined the effect of the ACE inhibitor, captopril (CAP), on the reversal of diet-induced obesity (DIO), insulin resistance and inflammation in mice. DIO was produced in C57BL/6J male mice (n=30) by maintaining animals on a high-fat diet (w/w 21% fat) for 12 weeks. During the subsequent 12-week treatment period, the animals were allowed access to the high-fat diet and either water containing CAP (0.05 mg ml(-1)) or plain tap water (CON, control). From the first week of treatment, food intake and body weight decreased in CAP-treated mice compared with CON mice. Both peripheral insulin sensitivity and hepatic insulin sensitivity were improved in CAP-treated mice compared with CON mice. CAP-treated mice had decreased absolute and relative liver and epididymal fat weights compared with CON mice. CAP-treated mice had higher plasma adiponectin and lower plasma leptin levels than CON mice. Relative to CON mice, CAP-treated mice had reduced adipose and skeletal muscle monocyte chemoattractant protein 1 (MCP-1), adipose interleukin-6 (IL-6), toll-like receptor 4 (TLR4) and uncoupling protein 2 (UCP2) mRNA expressions. Furthermore, CAP-treated mice had increased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), long chain acyl-CoA dehydrogenase (LCAD), hormone sensitive lipase (HSL) and decreased lipoprotein lipase (LPL) mRNA expressions in the liver. The results of the current study indicate that in mice with DIO, CAP treatment reduced food intake and body weight, improved insulin sensitivity and decreased the mRNA expression of markers of inflammation. Thus, CAP may be a viable treatment for obesity, insulin resistance and inflammation.
Publisher: Public Library of Science (PLoS)
Date: 27-07-2017
Publisher: Portland Press Ltd.
Date: 2004
DOI: 10.1042/CS20030116
Abstract: It has been speculated that creatine supplementation affects muscle glucose metabolism in humans by increasing muscle glycogen storage and up-regulating GLUT-4 protein expression. In the present study, we assessed the effects of creatine loading and prolonged supplementation on muscle glycogen storage and GLUT-4 mRNA and protein content in humans. A total of 20 subjects participated in a 6-week supplementation period during which creatine or a placebo was ingested. Muscle biopsies were taken before and after 5 days of creatine loading (20 g·day-1) and after 6 weeks of continued supplementation (2 g·day-1). Fasting plasma insulin concentrations, muscle creatine, glycogen and GLUT-4 protein content as well as GLUT-4, glycogen synthase-1 (GS-1) and glycogenin-1 (Gln-1) mRNA expression were determined. Creatine loading significantly increased total creatine, free creatine and creatine phosphate content with a concomitant 18±5% increase in muscle glycogen content (P& .05). The subsequent use of a 2 g·day-1 maintenance dose for 37 days did not maintain total creatine, creatine phosphate and glycogen content at the elevated levels. The initial increase in muscle glycogen accumulation could not be explained by an increase in fasting plasma insulin concentration, muscle GLUT-4 mRNA and/or protein content. In addition, neither muscle GS-1 nor Gln-1 mRNA expression was affected. We conclude that creatine ingestion itself stimulates muscle glycogen storage, but does not affect muscle GLUT-4 expression.
Publisher: Springer Science and Business Media LLC
Date: 20-02-2017
DOI: 10.1007/S00018-017-2481-5
Abstract: The mammalian target of rapamycin (mTOR) complex exerts a pivotal role in protein anabolism and cell growth. Despite its importance, few studies adequately address the complexity of phosphorylation of the mTOR protein itself to enable conclusions to be drawn on the extent of kinase activation following this event. In particular, a large number of studies in the skeletal muscle biology field have measured Serine 2448 (Ser2448) phosphorylation as a proxy of mTOR kinase activity. However, the evidence to be described is that Ser2448 is not a measure of mTOR kinase activity nor is a target of AKT activity and instead has inhibitory effects on the kinase that is targeted by the downstream effector p70S6K in a negative feedback loop mechanism, which is evident when revisiting muscle research studies. It is proposed that this residue modification acts as a fine-tuning mechanism that has been gained during vertebrate evolution. In conclusion, it is recommended that Ser2448 is an inadequate measure and that preferential analysis of mTORC1 activation should focus on the downstream and effector proteins, including p70S6K and 4E-BP1, along mTOR protein partners that bind to mTOR protein to form the active complexes 1 and 2.
Publisher: No publisher found
Date: 2020
DOI: 10.1007/S00592-019-01406-6
Abstract: Circulatory microRNAs (c-miRNAs) exert important roles in the molecular dysregulation of cardio-metabolic diseases. However, little is known whether dysregulated miRNA expression occurs when risk factors are elevated, as in the metabolic syndrome (MetS). This study quantified c-miRNA expression in in iduals with MetS compared to healthy, further examining the relationship of gene pathways with the underlying pathogenesis. Expression of 26 miRNAs was quantified in plasma from 40 women (20 healthy and 20 MetS) and 39 men (20 healthy and 19 MetS) by qPCR. In silico analysis was performed to investigate biological effects of the dysregulated miRNAs. Dysregulated miRNA expression was further validated in an independent cohort of 20 women (10 healthy and 10 MetS). Regression model adjusted for age and sex identified miR-15a-5p, miR-17-5p, miR-370-3p and miR-375 as important predictors of MetS presence. Analysis of predictive miRNAs in the validation cohort strengthened the relationship with miR-15a-5p and miR-17-5p expression. These miRNAs share genes involved in the regulation of metabolic pathways including insulin, wnt, fatty acid metabolism and AMPK. miR-15a-5p and miR-17-5p were identified as predictive biomarkers of MetS, irrespective of sexes, further demonstrating the relationship of c-miRNAs to known pathways of metabolic disturbances present in cardio-metabolic diseases.
Publisher: American Physiological Society
Date: 15-02-2015
Publisher: MDPI AG
Date: 14-02-2017
DOI: 10.3390/NU9020137
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.MEATSCI.2018.02.012
Abstract: Wagyu beef products are marketed as luxury goods to discerning consumers and the lipid content and composition are important drivers of wagyu product value. Wagyu beef is an extensively marbled meat product, well characterised for its tenderness and flavour. In New Zealand, pasture-fed Wagyu-dairy beef production is increasing to meet demand for ultra-premium meat products. Important for these characteristics is the composition of lipid species and their distribution across the carcass. The aim of this study was to analyse the distribution of fatty acids and phospholipids in 26 table cuts, nine co-products and three fat deposits of carcasses from New Zealand pasture-fed Wagyu-dairy cross beef carcasses (n = 5). Phospholipid and fatty acid levels varied across different cuts of the carcass, but typically cuts with high levels of phospholipids also had high levels of omega-3 fatty acids and low levels of saturated fatty acids. This work will be used in the future to examine the potential health aspects of pasture-fed Wagyu beef.
Publisher: Elsevier BV
Date: 12-2011
Publisher: Public Library of Science (PLoS)
Date: 27-07-2012
Publisher: Canadian Science Publishing
Date: 02-2012
DOI: 10.1139/H11-132
Abstract: Purpose: To investigate the impact of whey protein ingestion and resistance exercise training on the phosphorylation of mRNA translational signalling proteins in the skeletal muscle of young and old men. Methods: Sixteen healthy young (aged 18–25 years) and 15 healthy older men (aged 60–75 years) completed 12 weeks of resistance exercise and were randomly assigned to consume a whey protein (WPI) or placebo drink after each session. Muscle biopsies were collected before and 2 h after an acute exercise bout at the beginning and the end of training. Results: All subjects significantly increased strength after following strength training. Phosphorylation of mTOR was significantly greater in the WPI groups compared with placebo for both younger and older subjects. Phosphorylation of p70 S6K , eIF4G, and 4EBP1 was greater for older subjects consuming WPI. Phosphorylation of rpS6, eIF4G, and 4EBP1 tended to increase in the younger subjects that had consumed WPI. Post-training, younger subjects demonstrated a similar pattern of mTOR phosphorylation as seen pre-training. In contrast, the initial heightened phosphorylation of mTOR, p70 S6K , rpS6, and eIF4G in older muscle to combined resistance exercise and WPI ingestion became less pronounced after repeated training sessions. Conclusions: In the untrained state, resistance exercise coupled with WPI increases the phosphorylation of proteins involved in mRNA translation compared with exercise alone. Post-training, WPI- and exercise-induced protein phosphorylation was reduced in older men, but not in younger men. Thus, strategies to induce hypertrophy should utilize protein and resistance training concurrently. Further investigations should delineate interventions that will maintain sensitivity to anabolic stimuli in older populations.
Publisher: MDPI
Date: 13-12-2019
Publisher: MDPI AG
Date: 07-2015
DOI: 10.3390/NU7075224
Publisher: Springer Science and Business Media LLC
Date: 29-07-2021
DOI: 10.1038/S41390-020-1069-1
Abstract: Infants born moderate to late preterm constitute the majority of preterm births, yet guidelines for their nutritional care are unclear. Maternal milk is the most appropriate nutrition for these infants however, its composition can be influenced by environmental factors. The present study therefore investigated perinatal predictors of human milk composition in a preterm cohort. Milk was collected during the DIAMOND trial (DIfferent Approaches to Moderate and late preterm Nutrition: Determinants of feed tolerance, body composition and development) from 169 mothers of 191 infants at three time-points (5 and 10 days post partum and 4 months' corrected age). Leptin, adiponectin and insulin-like growth factor-1 (IGF-1) were analysed by enzyme-linked immunosorbent assay. Generalised mixed models were used to evaluate associations between milk composition and maternal/infant erinatal factors. Most findings were independent of collection time-point. Gestational diabetes was associated with lower adiponectin. Higher adiponectin and lower leptin were associated with higher socioeconomic status, higher maternal education and ability to fully breastfeed at discharge from hospital. Higher leptin was associated with high perceived stress during hospital admission. Milk IGF-1 displayed sex-specific patterns in association with maternal social deprivation. Maternal, infant and environmental factors during the perinatal period were associated with milk compositional profiles throughout lactation. Further clinical trials should investigate the impact of such changes in terms of long-term infant outcomes. Human milk is the best nutrition for the infant. However, its composition may be susceptible to alterations determined by pathological conditions mother and infant may face throughout pregnancy and in the perinatal period. This study found that perinatal factors are associated with human milk composition from early to late lactation. If human milk composition throughout lactation is "programmed" during pregnancy or early lactation, infants who were exposed in utero to environmental insults may still be exposed to them during lactation. The impact of human milk compositional alteration on infant growth following perinatal pathological events requires further investigation.
Publisher: Springer Science and Business Media LLC
Date: 26-04-2011
DOI: 10.1038/IJO.2011.85
Abstract: Brown adipose tissue mitochondria express the unique thermogenic uncoupling protein-1. Recently, brown adipocyte progenitors have been identified in the CD34+ cell population of human skeletal muscle. The aims of this study were firstly to determine if obesity and diabetes have altered amounts of muscle brown adipocyte progenitors and, secondly, to establish if the latter are correlated with clinical parameters of obesity and diabetes. Body mass index (BMI), plasma glucose, insulin, cholesterol and triglycerides as well as homeostasis model assessment were measured in lean (n=10), obese (n=18) and obese-diabetic (n=15) subjects and muscle biopsies were taken from the rectus abdominus. CD34 being also expressed on endothelial cells, we measured CD31, another endothelial marker, and expressed the brown adipocyte progenitors, as the CD34/CD31 mRNA ratio. The latter was significantly reduced in the obese vs lean subjects suggesting a smaller pool of brown adipocyte progenitors. More strikingly, for lean and obese subjects negative correlations were observed between the CD34/CD31 mRNA ratios and BMI, fasting insulin levels and homeostasis model assessment. These correlations highlight the potential physiological relevance of the muscle CD34/CD31 mRNA ratio.
Publisher: MDPI AG
Date: 28-11-2019
DOI: 10.3390/NU11122893
Abstract: B-vitamin deficiency is common in ageing populations either due to altered dietary habits or altered digestive and metabolic functions. There is limited data on the acute circulating concentrations of B-vitamins and their various forms (vitamers), following ingestion of realistic meals. This study compared the acute circulating B-vitamin and vitamer responses to either an energy-dense (ED) or a nutrient-dense (ND) breakfast meal, consumed in a randomized cross-over sequence, in older and younger adults (n = 15 and 15, aged 67.3 ± 1.5 and 22.7 ± 0.5 years (mean ± SEM), respectively). Eleven differing B-vitamins and vitamers were determined in plasma s les by ultra-high-performance liquid chromatography-tandem mass spectrometry, in the fasting and postprandial state (hourly for 5 h). While postprandial thiamine concentration increased following both meals, riboflavin increased only following a ND meal in both age groups. Many vitamins including nicotinic acid, pantothenic acid, pyridoxal, pyridoxamine, pyridoxal-5’phosphate, and 4-pyridoxic acid remained unaltered, and flavin mononucleotide (FMN), nicotinamide and nicotinuric acid concentrations reduced following both meals. Biological age and food composition had minimal impact on postprandial B-vitamin concentrations, yet the differences between the ED and ND meals for riboflavin highlight the importance of riboflavin intake to achieve adequacy.
Publisher: American Physiological Society
Date: 02-2019
DOI: 10.1152/JAPPLPHYSIOL.00777.2018
Abstract: Measurement of skeletal muscle mitochondrial respiration requires invasive biopsy to obtain a muscle s le. Peripheral blood mononuclear cell (PBMC) mitochondrial protein content appears to reflect training status in young men however, no studies have investigated whether there are training-induced changes in PBMC mitochondrial respiration. Therefore, we determined whether PBMC mitochondrial respiration could be used as a marker of skeletal muscle mitochondrial respiration in young healthy men and whether PBMC mitochondrial respiration responds to short-term training. Skeletal muscle and PBMC s les from 10 healthy young (18–35 yr) male participants were taken before and after a 2-wk high-intensity interval training protocol. High-resolution respirometry was used to determine mitochondrial respiration from muscle and PBMCs, and Western blotting and quantitative PCR were used to assess mitochondrial biogenesis in PBMCs. PBMC mitochondrial respiration was not correlated with muscle mitochondrial respiration at baseline ( R 2 = 0.012–0.364, P 0.05). While muscle mitochondrial respiration increased in response to training (32.1–61.5%, P 0.05), PBMC respiration was not affected by training. Consequently, PBMCs did not predict training effect on muscle mitochondrial respiration ( R 2 = 0.024–0.283, P 0.05). Similarly, gene and protein markers of mitochondrial biogenesis did not increase in PBMCs following training. This suggests PBMC mitochondrial function does not reflect that of skeletal muscle and does not increase following short-term high-intensity training. PBMCs are therefore not a suitable biomarker for muscle mitochondrial function in young healthy men. It may be useful to study PBMC mitochondrial function as a biomarker of muscle mitochondrial function in pathological populations with different respiration capacities. NEW & NOTEWORTHY Research in primates has suggested that peripheral blood mononuclear cells (PBMCs) may provide a less-invasive alternative to a muscle biopsy for measuring muscle mitochondrial function. Furthermore, trained in iduals appear to have greater mitochondrial content in PBMCs. Here we show that in healthy young men, PBMCs do not reflect skeletal muscle mitochondrial function and do not adapt in response to a training intervention that increases muscle mitochondrial function, suggesting PBMCs are a poor marker of muscle mitochondrial function in humans.
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.PLEFA.2013.01.010
Abstract: The study of the metabolism of docosapentaenoic acid (DPA, 22:5n-3) in humans has been limited by the unavailability of pure DPA and the fact that DPA is found in combination with eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) in natural products. In this double blind cross over study, pure DPA and EPA were incorporated in meals served to healthy female volunteers. Mass spectrometric methods were used to study the chylomicron lipidomics. Plasma chylomicronemia was significantly reduced after the meal containing DPA compared with the meal containing EPA or olive oil only. Both EPA and DPA were incorporated into chylomicron TAGs, while there was less incorporation into chylomicron phospholipids. Lipidomic analysis of the chylomicron TAGs revealed the dynamic nature of chylomicron TAGs. The main TAG species that EPA and DPA were incorporated into were EPA/18:1/18:1, DPA/18:1/16:0 and DPA/18:1/18:1. There was very limited conversion of DPA and EPA to DHA and there were no increases in EPA levels during the 5h postprandial period after the DPA meal. In conclusion, EPA and DPA showed different metabolic fates, and DPA hindered the digestion, ingestion or incorporation into chylomicrons of the olive oil present in the meal.
Publisher: Frontiers Media SA
Date: 15-09-1970
Publisher: MDPI AG
Date: 22-05-2018
Publisher: Wiley
Date: 20-08-2012
DOI: 10.1002/MUS.23317
Abstract: This study compared changes in myokine and myogenic genes following resistance exercise (3 sets of 12 repetitions of maximal unilateral knee extension) in 20 elderly men (67.8 ± 1.0 years) and 15 elderly women (67.2 ± 1.5 years). Monocyte chemotactic protein (MCP)-1, macrophage inhibitory protein (MIP)-1β, interleukin (IL)-6 and MyoD mRNA increased significantly (P < 0.05), whereas myogenin and myostatin mRNA decreased significantly after exercise in both groups. Macrophage-1 (Mac-1) and MCP-3 mRNA did not change significantly after exercise in either group. MIP-1β, Mac-1 and myostatin mRNA were significantly higher before and after exercise in men compared with women. In contrast, MCP-3 and myogenin mRNA were significantly higher before and after exercise in the women compared with the men. In elderly in iduals, gender influences the mRNA expression of certain myokines and growth factors, both at rest and after resistance exercise. These differences may influence muscle regeneration following muscle injury.
Publisher: Informa UK Limited
Date: 2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2019
DOI: 10.1249/MSS.0000000000001775
Abstract: To investigate the effects of blood flow–restricted resistance exercise (BFRRE) on myofiber areas (MFA), number of myonuclei and satellite cells (SC), muscle size and strength in powerlifters. Seventeen national level powerlifters (25 ± 6 yr [mean ± SD], 15 men) were randomly assigned to either a BFRRE group ( n = 9) performing two blocks (weeks 1 and 3) of five BFRRE front squat sessions within a 6.5-wk training period, or a conventional training group (Con n = 8) performing front squats at 60%–85% of one-repetition maximum (1RM). The BFRRE consisted of four sets (first and last set to voluntary failure) at ~30% of 1RM. Muscle biopsies were obtained from m. vastus lateralis (VL) and analyzed for MFA, myonuclei, SC and capillaries. Cross-sectional areas (CSA) of VL and m. rectus femoris were measured by ultrasonography. Strength was evaluated by maximal voluntary isokinetic torque (MVIT) in knee extension and 1RM in front squat. BFRRE induced selective increases in type I MFA (BFRRE: 12% vs Con: 0%, P 0.01) and myonuclear number (BFRRE: 18% vs Con: 0%, P = 0.02). Type II MFA was unaltered in both groups. BFRRE induced greater changes in VL CSA (7.7% vs 0.5%, P = 0.04), which correlated with the increases in MFA of type I fibers ( r = 0.81, P = 0.02). No group differences were observed in SC and strength changes, although MVIT increased with BFRRE ( P = 0.04), whereas 1RM increased in Con ( P = 0.02). Two blocks of low-load BFRRE in the front squat exercise resulted in increased quadriceps CSA associated with preferential hypertrophy and myonuclear addition in type 1 fibers of national level powerlifters.
Publisher: American Physiological Society
Date: 10-2018
DOI: 10.1152/AJPENDO.00138.2018
Abstract: MicroRNAs (miRNAs) regulate gene expression via transcript degradation and translational inhibition, and they may also function as long distance signaling molecules. Circulatory miRNAs are either protein-bound or packaged within vesicles (exosomes). Ten young men (24.6 ± 4.0 yr) underwent a single bout of high-intensity interval cycling exercise. Vastus lateralis biopsies and plasma were collected immediately before and after exercise, as well as 4 h following the exercise bout. Twenty-nine miRNAs previously reported to be regulated by acute exercise were assessed within muscle, venous plasma, and enriched circulatory exosomes via qRT-PCR. Of the 29 targeted miRNAs, 11 were altered in muscle, 8 in plasma, and 9 in the exosome fraction. Although changes in muscle and plasma expression were bidirectional, all regulated exosomal miRNAs increased following exercise. Three miRNAs were altered in all three s le pools (miR-1-3p, -16-5p, and -222-3p), three in both muscle and plasma (miR-21-5p, -134-3p, and -107), three in both muscle and exosomes (miR-23a-3p, -208a-3p, and -150-5p), and three in both plasma and exosomes (miR-486-5p, -126-3p, and -378a-5p). There was a marked discrepancy between the observed alterations between s le pools. A subset of exosomal miRNAs increased in abundance following exercise, suggesting an exercise-induced release of exosomes enriched in specific miRNAs. The uniqueness of the exosomal miRNA response suggests its relevance as a s le pool that needs to be further explored in better understanding biological functions.
Publisher: Elsevier BV
Date: 06-1994
DOI: 10.1016/0026-0495(94)90122-8
Abstract: Undigested carbohydrates and some dietary fibers are fermented in the large intestine to form short-chain fatty acids (SCFA), including acetate, propionate, and butyrate. It has been suggested that some of the beneficial effects of high-carbohydrate, high-fiber diets on carbohydrate and lipid metabolism are mediated by the metabolism of SCFA in the liver. Propionate has been shown in vitro to decrease glucose production in rat hepatocytes. The aim of the present study was to investigate the effects of propionate on carbohydrate metabolism in normal and streptozocin (STZ)-induced diabetic male Sprague-Dawley rats. Rats were fed a high-fat diet with or without sodium propionate supplementation (either 0.5% or 5% wt/wt) for 4 weeks. At the completion of the feeding period, body weight and liver glycogen concentrations were significantly decreased in STZ-diabetic rats and were unaffected by propionate supplementation. Although STZ-diabetic animals had elevated fasting plasma glucose, cholesterol, and triglyceride levels relative to nondiabetic rats, propionate supplementation had no significant effect on these parameters in either group. Basal and insulin-stimulated carbohydrate metabolism were assessed using the euglycemic cl technique in overnight-fasted animals with 3(H)-6-glucose infusion. As expected, basal hepatic glucose production (HGP) was higher and the metabolic clearance rate of glucose (MCR) was lower in STZ-diabetic rats. High-dose insulin infusion (3 mU.kg-1.min-1) suppressed HGP in nondiabetic and diabetic animals and increased the MCR in nondiabetic animals. However, propionate supplementation did not alter basal or insulin-stimulated HGP or the MCR in either nondiabetic or diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 18-11-2008
DOI: 10.1113/EXPPHYSIOL.2008.042796
Abstract: Exercise increases Na(+)-K(+) pump isoform gene expression and elevates muscle reactive oxygen species (ROS). We investigated whether enhanced ROS scavenging induced with the antioxidant N-acetylcysteine (NAC) blunted the increase in Na(+)-K(+) pump mRNA during repeated contractions in human and rat muscle. In experiment 1, well-trained subjects received saline or NAC intravenously prior to and during 45 min cycling. Vastus lateralis muscle biopsies were taken pre-infusion and following exercise. In experiment 2, isolated rat extensor digitorum longus muscles were pre-incubated without or with 10 mm NAC and then rested or stimulated electrically at 60 Hz for 90 s. After 3 h recovery, muscles were frozen. In both experiments, the muscles were analysed for Na(+)-K(+) pump alpha(1), alpha(2), alpha(3), beta(1), beta(2) and beta(3) mRNA. In experiment 1, exercise increased alpha(2) mRNA by 1.0-fold (P = 0.03), but alpha(2) mRNA was reduced by 0.40-fold with NAC (P = 0.03). Exercise increased alpha(3), beta(1) and beta(2) mRNA by 2.0- to 3.4-fold (P 0.32). Neither exercise nor NAC altered alpha(1) or beta(3) mRNA (P > 0.31). In experiment 2, electrical stimulation increased alpha(1), alpha(2) and alpha(3) mRNA by 2.3- to 17.4-fold (P 0.07). Electrical stimulation almost completely reduced beta(1) mRNA but only in the presence of NAC (P 0.09). In conclusion, NAC attenuated the increase in Na(+)-K(+) pump alpha(2) mRNA with exercise in human muscle and all alpha isoforms with electrical stimulation in rat muscle. This indicates a regulatory role for ROS in Na(+)-K(+) pump alpha isoform mRNA in mammalian muscle during repeated contractions.
Publisher: Mary Ann Liebert Inc
Date: 05-2010
Abstract: We investigated the effect of carbohydrate ingestion after maximal lengthening contractions of the knee extensors on circulating concentrations of myocellular proteins and cytokines, and cytokine mRNA expression in muscle. Using a cross-over design, 10 healthy males completed 5 sets of 10 lengthening (eccentric) contractions (unilateral leg press) at 120% 1 repetition-maximum. Subjects were randomized to consume a carbohydrate drink (15% weight per volume 3 g/kg BM) for 3 h after exercise using one leg, or a placebo drink after exercise using the contralateral leg on another day. Blood s les (10 mL) were collected before exercise and after 0, 30, 60, 90, 120, 150, and 180 min of recovery. Muscle biopsies (vastus lateralis) were collected before exercise and after 3 h of recovery. Following carbohydrate ingestion, serum concentrations of glucose (30-90 min and at 150 min) and insulin (30-180 min) increased (P < 0.05) above pre-exercise values. Serum myoglobin concentration increased ( approximately 250% P < 0.05) after both trials. In contrast, serum cytokine concentrations were unchanged throughout recovery in both trials. Muscle mRNA expression for IL-8 (6.4-fold), MCP-1 (4.7-fold), and IL-6 (7.3-fold) increased substantially after carbohydrate ingestion. TNF-alpha mRNA expression did not change after either trial. Carbohydrate ingestion during early recovery from exercise-induced muscle injury may promote proinflammatory reactions within skeletal muscle.
Publisher: American Physiological Society
Date: 08-2021
DOI: 10.1152/JAPPLPHYSIOL.00115.2020
Abstract: BFRRE has been reported to preferentially stress type I muscle fibers, as evidenced by HSP responses. We extend these findings by showing that the HSP responses occur in both fiber types but more so in type I fibers and that they can still be induced after a short-term training period. Furthermore, the reductions in glycogen content of type I fibers after strenuous frequent BFRRE in unaccustomed subjects can be prolonged (≥5 days), probably due to microdamage.
Publisher: Wiley
Date: 03-2002
DOI: 10.1046/J.1440-1681.2002.03621.X
Abstract: 1. Skeletal muscle is a complex and heterogenous tissue capable of remarkable adaptation in response to exercise training. The role of gene transcription, as an initial target to control protein synthesis, is poorly understood. 2. Mature myofibres contain several hundred nuclei, all of which maintain transcriptional competency, although the localized responsiveness of nuclei is not well known. Myofibres are capable of hypertrophy. These processes require the activation and myogenic differentiation of mononuclear satellite cells that fuse with the enlarging or repairing myofibre. 3. A single bout of exercise in human subjects is capable of activating the expression of many erse groups of genes. 4. The impact of repeated exercise bouts, typical of exercise training, on gene expression has yet to receive systematic investigation. 5. The molecular programme elicited by resistance exercise and endurance exercise differs markedly. Muscular hypertrophy following resistance exercise is dependent on the activation of satellite cells and their subsequent myogenic maturation. Endurance exercise requires the simultaneous activation of mitochondrial and nuclear genes to enable mitochondrial biogenesis. 6. Future analysis of the regulation of genes by exercise may combine high-throughput technologies, such as gene-chips, enabling the rapid detection and analysis of changes in the expression of many thousands of genes.
Publisher: JMIR Publications Inc.
Date: 21-12-2021
DOI: 10.2196/30909
Abstract: The trend of flexitarian eating patterns is on the rise, with young adults among the biggest adopters claiming health and environmental reasons to reduce red meat intake. Nutrient-dense meat and animal products are often the lynchpin of these diets, even when consumed only occasionally and in moderate amounts. Red meat provides forms and concentrations of essential proteins, lipids, and micronutrients that are scarce in exclusively vegetarian regimens. The aim of this study is to consider the effects of moderate consumption of lean red meat as part of an otherwise vegetarian balanced diet and its impact on biomarkers of sustained health and well-being. A cohort of healthy, young (20-34 years old, n=80) male and female participants will take part in a 2-arm, parallel randomized controlled trial (RCT) for a duration of 12 weeks, with a 3-month posttrial follow-up. The trial will commence with a 2-week assessment period followed by allocation to the intervention arms. The intervention will include the consumption of red meat or meat alternatives 3 times per week for 10 weeks. Blood s les of the participants will be collected to measure changes in erythrocyte fatty acid distribution, circulating amino acids, neurotransmitters, markers of mineral status, and inflammatory markers. Questionnaires to assess well-being and mental health will be undertaken every 2 weeks. Body composition, physical function, and blood parameters will be assessed at allocation (t0), week 5 into the intervention (t5), and post intervention (t10). The protocol has been developed using the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) checklist and the outcomes will be reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines. The trial was approved by the New Zealand Ministry of Health’s Health and Disability Ethics Committees (protocol 20/STH/157). The results of this study will be communicated via publication. To our knowledge, this is the first RCT investigating the overarching health consequences of consuming pasture-fed red meat or no meat as part of a healthy diet. ClinicalTrials.gov NCT04869163 t2/show/NCT04869163 PRR1-10.2196/30909
Publisher: American Physiological Society
Date: 07-2015
DOI: 10.1152/AJPENDO.00050.2015
Abstract: Resistance training (RT) has the capacity to increase skeletal muscle mass, which is due in part to transient increases in the rate of muscle protein synthesis during postexercise recovery. The role of ribosome biogenesis in supporting the increased muscle protein synthetic demands is not known. This study examined the effect of both a single acute bout of resistance exercise (RE) and a chronic RT program on the muscle ribosome biogenesis response. Fourteen healthy young men performed a single bout of RE both before and after 8 wk of chronic RT. Muscle cross-sectional area was increased by 6 ± 4.5% in response to 8 wk of RT. Acute RE-induced activation of the ERK and mTOR pathways were similar before and after RT, as assessed by phosphorylation of ERK, MNK1, p70S6K, and S6 ribosomal protein 1 h postexercise. Phosphorylation of TIF-IA was also similarly elevated following both RE sessions. Cyclin D1 protein levels, which appeared to be regulated at the translational rather than transcriptional level, were acutely increased after RE. UBF was the only protein found to be highly phosphorylated at rest after 8 wk of training. Also, muscle levels of the rRNAs, including the precursor 45S and the mature transcripts (28S, 18S, and 5.8S), were increased in response to RT. We propose that ribosome biogenesis is an important yet overlooked event in RE-induced muscle hypertrophy that warrants further investigation.
Publisher: American Physiological Society
Date: 08-2015
DOI: 10.1152/AJPREGU.00031.2015
Abstract: This study investigated the effect of regular postexercise cold water immersion (CWI) on muscle aerobic adaptations to endurance training. Eight males performed 3 sessions/wk of endurance training for 4 wk. Following each session, subjects immersed one leg in a cold water bath (10°C COLD) for 15 min, while the contralateral leg served as a control (CON). Muscle biopsies were obtained from vastus lateralis of both CON and COLD legs prior to training and 48 h following the last training session. S les were analyzed for signaling kinases: p38 MAPK and AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), enzyme activities indicative of mitochondrial biogenesis, and protein subunits representative of respiratory chain complexes I–V. Following training, subjects' peak oxygen uptake and running velocity were improved by 5.9% and 6.2%, respectively ( P 0.05). Repeated CWI resulted in higher total AMPK, phosphorylated AMPK, phosphorylated acetyl-CoA carboxylase, β-3-hydroxyacyl-CoA-dehydrogenase and the protein subunits representative of complex I and III ( P 0.05). Moreover, large effect sizes (Cohen's d 0.8) were noted with changes in protein content of p38 ( d = 1.02, P = 0.064), PGC-1α ( d = 0.99, P = 0.079), and peroxisome proliferator-activated receptor α ( d = 0.93, P = 0.10) in COLD compared with CON. No differences between conditions were observed in the representative protein subunits of respiratory complexes II, IV, and V and in the activities of several mitochondrial enzymes ( P 0.05). These findings indicate that regular CWI enhances p38, AMPK, and possibly mitochondrial biogenesis.
Publisher: Wiley
Date: 03-02-2020
DOI: 10.1113/EP087995
Publisher: MDPI AG
Date: 22-11-2020
DOI: 10.3390/NU12113579
Abstract: Dietary intake of iron is known to be associated with impaired glucose metabolism. However, its involvement in derangements of glucose metabolism after acute pancreatitis (AP) is not completely understood. The aim was to investigate the association between dietary iron intake and markers of glucose metabolism in in iduals after an attack of AP. Fasting blood s les were collected to analyse markers of glucose metabolism (fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c)). The EPIC-Norfolk food frequency questionnaire was used to determine the habitual intake of dietary iron (total, haem, and non-haem). Multivariable linear regression analyses were conducted and six statistical models were built to adjust for covariates. A total of 109 in iduals after AP were studied in a cross-sectional fashion. Total iron (β (95% confidence interval) = −0.19 (−0.35, −0.05) p = 0.01 in the most adjusted model) and non-haem iron (β (95% confidence interval) = −0.19 (−0.33, −0.04) p = 0.03 in the most adjusted model) were significantly associated with FPG, consistently in all adjusted model. Total iron and non-haem iron did not have consistent significant associations with HbA1c. Dietary haem iron intake was not associated with either FPG or HbA1c. Habitual intake of dietary iron is inversely associated with FPG in in iduals after an attack of AP and may be involved in the pathogenesis of new-onset diabetes after pancreatitis. Prospective longitudinal studies are now warranted to unveil the specific mechanism underlying the involvement of dietary iron.
Publisher: MDPI AG
Date: 12-09-2019
DOI: 10.3390/NU11092207
Abstract: Higher dietary protein intake is increasingly recommended for the elderly however, high protein diets have also been linked to increased cardiovascular disease (CVD) risk. Trimethylamine-N-oxide (TMAO) is a bacterial metabolite derived from choline and carnitine abundant from animal protein-rich foods. TMAO may be a novel biomarker for heightened CVD risk. The purpose of this study was to assess the impact of a high protein diet on TMAO. Healthy men (74.2 ± 3.6 years, n = 29) were randomised to consume the recommended dietary allowance of protein (RDA: 0.8 g protein/kg bodyweight/day) or twice the RDA (2RDA) as part of a supplied diet for 10 weeks. Fasting blood s les were collected pre- and post-intervention for measurement of TMAO, blood lipids, glucose tolerance, insulin sensitivity, and inflammatory biomarkers. An oral glucose tolerance test was also performed. In comparison with RDA, the 2RDA diet increased circulatory TMAO (p = 0.002) but unexpectedly decreased renal excretion of TMAO (p = 0.003). LDL cholesterol was increased in 2RDA compared to RDA (p = 0.049), but no differences in other biomarkers of CVD risk and insulin sensitivity were evident between groups. In conclusion, circulatory TMAO is responsive to changes in dietary protein intake in older healthy males.
Publisher: MDPI AG
Date: 15-10-2018
DOI: 10.3390/NU10101510
Abstract: Dairy, as a major component of a high protein diet, is a critical dietary source of branched chain amino acids (BCAA), which are biomarkers of health and diseases. While BCAA are known to be key stimulators of protein synthesis, elevated circulatory BCAA is an independent risk factor for type 2 diabetes mellitus. This study examined the impact of altered dairy intake on plasma BCAA and their potential relationship to insulin sensitivity. Healthy adults (n = 102) were randomized to receive dietary advice to reduce, maintain, or increase habitual dairy intake for 1 month. Food intake was recorded with food frequency questionnaires. Self-reported protein intake from dairy was reported to be reduced (−14.6 ± 3.0 g/day), maintained (−4.0 ± 2.0 g/day) or increased (+13.8 ± 4.1 g/day) according to group allocation. No significant alterations in circulating free amino acids (AA), including BCAA, were measured. Insulin sensitivity, as assessed by homeostatic model assessment-insulin resistance (HOMA-IR), was also unaltered. A significant change in dairy protein intake showed no significant effect on fasting circulatory BCAA and insulin sensitivity in healthy populations.
Publisher: American Physiological Society
Date: 06-2010
DOI: 10.1152/AJPREGU.00467.2009
Abstract: The world's elderly population is expanding rapidly, and we are now faced with the significant challenge of maintaining or improving physical activity, independence, and quality of life in the elderly. Counteracting the progressive loss of muscle mass that occurs in the elderly, known as sarcopenia, represents a major hurdle in achieving these goals. Indirect evidence for a role of inflammation in sarcopenia is that markers of systemic inflammation correlate with the loss of muscle mass and strength in the elderly. More direct evidence is that compared with skeletal muscle of young people, the number of macrophages is lower, the gene expression of several cytokines is higher, and stress signaling proteins are activated in skeletal muscle of elderly people at rest. Sarcopenia may also result from inadequate repair and chronic maladaptation following muscle injury in the elderly. Macrophage infiltration and the gene expression of certain cytokines are reduced in skeletal muscle of elderly people compared with young people following exercise-induced muscle injury. Further research is required to identify the cause(s) of inflammation in skeletal muscle of elderly people. Additional work is also needed to expand our understanding of the cells, proteins, and transcription factors that regulate inflammation in the skeletal muscle of elderly people at rest and after exercise. This knowledge is critical for devising strategies to restrict sarcopenia, and improve the health of today's elderly population.
Publisher: Cambridge University Press (CUP)
Date: 15-01-2016
DOI: 10.1017/S000711451500505X
Abstract: Ageing is associated with a prolonged and exaggerated postprandial lipaemia. This study aimed to examine the contribution of alterations in chylomicron synthesis, size and lipid composition to increased lipaemia. Healthy older (60–75 years n 15) and younger (20–25 years n 15) subjects consumed a high-fat breakfast. Chylomicron dynamics and fatty acid composition were analysed for 5 h in the postprandial state. Plasma TAG levels were elevated following the meal in the older subjects, relative to younger subjects ( P ·01). For older subjects compared with younger subjects, circulating chylomicron particle size was smaller ( P ·05), with greater apoB content ( P ·05) at all postprandial time points. However, total chylomicron TAG concentration between the groups was unaltered post-meal. Compared with younger subjects, the older subjects exhibited a greater proportion of oleic acid in the TAG and phospholipid (PL) fraction ( P ·05), plus lower proportions of linoleic acid in the TAG fraction of the chylomicrons ( P ·01). Thus, following the ingestion of a high-fat meal, older in iduals demonstrate both smaller, more numerous chylomicrons, with a greater total MUFA and lower PUFA contents. These data suggest that the increased postprandial lipaemia of ageing cannot be attributed to increased chylomicron TAG. Rather, ageing is associated with changes in chylomicron particle size, apoB content and fatty acid composition of the chylomicron TAG and PL fractions.
Publisher: Wiley
Date: 19-01-2007
DOI: 10.1111/J.1748-1716.2006.01635.X
Abstract: This study investigated the effects of endurance training status and sex differences on skeletal muscle Na+,K+-pump mRNA expression, content and activity. Forty-five endurance-trained males (ETM), 11 recreationally active males (RAM), and nine recreationally active females (RAF) underwent a vastus lateralis muscle biopsy. Muscle was analysed for Na+,K+-pump alpha1, alpha2, alpha3, beta1, beta2 and beta3 isoform mRNA expression (real-time reverse transcription-polymerase chain reaction), content ([3H]-ouabain-binding site) and maximal activity (3-O-methylfluorescein phosphatase, 3-O-MFPase). ETM demonstrated lower alpha1, alpha3, beta2 and beta3 mRNA expression by 74%, 62%, 70% and 82%, respectively, than RAM (P<0.04). In contrast, [3H]-ouabain binding and 3-O-MFPase activity were each higher in ETM than in RAM, by 16% (P<0.03). RAM demonstrated a 230% and 364% higher alpha3 and beta3 mRNA expression than RAF, respectively (P<0.05), but no significant sex differences were found for alpha1, alpha2, beta1 or beta2 mRNA, [3H]-ouabain binding or 3-O-MFPase activity. No significant correlation was found between years of endurance training and either [3H]-ouabain binding or 3-O-MFPase activity. Significant but weak correlations were found between the number of training hours per week and 3-O-MFPase activity (r=0.31, P<0.02) and between incremental exercise VO2(peak)) and both [3H]-ouabain binding (r=0.33, P<0.01) and 3-O-MFPase activity (r=0.28, P<0.03). Isoform-specific differences in Na+,K+-pump mRNA expression were found with both training status and sex differences, but only training status influenced Na+,K+-pump content and maximal activity in human skeletal muscle.
Publisher: Springer Science and Business Media LLC
Date: 05-04-2017
Publisher: The Endocrine Society
Date: 06-2005
DOI: 10.1210/JC.2004-1980
Abstract: Adiponectin is an adipocyte-derived hormone associated with antidiabetic actions. In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2. In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects. Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052). In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside. In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation. In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation however, ACCbeta phosphorylation and fatty acid oxidation were unaffected. Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1. These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2015
DOI: 10.1007/S12603-015-0500-5
Abstract: To measure the postprandial plasma amino acid appearance in younger and older adults following a high protein mixed meal. Cross-sectional study. Clinical research setting. Healthy men and women aged 60-75 (n=15) years, and young controls aged 20-25 years (n=15) matched for body mass index and insulin sensitivity based on the homeostatic model assessment of insulin resistance. High protein mixed meal of complete food products. Circulating amino acid concentrations were determined hourly before and for 5 hours after meal ingestion. There was no difference between cohorts in postprandial appearance of non-essential amino acids, or area under the curve of any in idual amino acid or amino acid class. However, older adults had higher baseline concentrations of aspartic acid, glutamic acid, glycine, ornithine, threonine and tyrosine and lower baseline concentrations of hydroxyproline, isoleucine, leucine, methionine and valine compared to younger adults. Younger adults showed peak essential (EAA) and branched-chain amino acid (BCAA) concentrations at 1 hour post meal while older adults' peak EAA and BCAA concentration was at 3 hours. Similarly, peak total amino acid concentrations were at 3 hours in older adults. Older adults digested and absorbed the protein within a mixed meal more slowly than younger adults. Delayed absorption of AA following a mixed meal of complete food products may suppress or delay protein synthesis in senescent muscle.
Publisher: American Physiological Society
Date: 05-2006
DOI: 10.1152/AJPENDO.00299.2005
Abstract: Skeletal muscle displays enormous plasticity to respond to contractile activity with muscle from strength- (ST) and endurance-trained (ET) athletes representing erse states of the adaptation continuum. Training adaptation can be viewed as the accumulation of specific proteins. Hence, the altered gene expression that allows for changes in protein concentration is of major importance for any training adaptation. Accordingly, the aim of the present study was to quantify acute subcellular responses in muscle to habitual and unfamiliar exercise. After 24-h diet/exercise control, 13 male subjects (7 ST and 6 ET) performed a random order of either resistance (8 × 5 maximal leg extensions) or endurance exercise (1 h of cycling at 70% peak O 2 uptake). Muscle biopsies were taken from vastus lateralis at rest and 3 h after exercise. Gene expression was analyzed using real-time PCR with changes normalized relative to preexercise values. After cycling exercise, peroxisome proliferator-activated receptor-γ coactivator-1α (ET ∼8.5-fold, ST ∼10-fold, P 0.001), pyruvate dehydrogenase kinase-4 (PDK-4 ET ∼26-fold, ST ∼39-fold), vascular endothelial growth factor (VEGF ET ∼4.5-fold, ST ∼4-fold), and muscle atrophy F-box protein (MAFbx) (ET ∼2-fold, ST ∼0.4-fold) mRNA increased in both groups, whereas MyoD (∼3-fold), myogenin (∼0.9-fold), and myostatin (∼2-fold) mRNA increased in ET but not in ST ( P 0.05). After resistance exercise PDK-4 (∼7-fold, P 0.01) and MyoD (∼0.7-fold) increased, whereas MAFbx (∼0.7-fold) and myostatin (∼0.6-fold) decreased in ET but not in ST. We conclude that prior training history can modify the acute gene responses in skeletal muscle to subsequent exercise.
Publisher: American Physiological Society
Date: 09-2006
DOI: 10.1152/JAPPLPHYSIOL.01489.2005
Abstract: To examine the influence of exercise intensity on the increases in vastus lateralis GLUT4 mRNA and protein after exercise, six untrained men exercised for 60 min at 39 ± 3% peak oxygen consumption (V̇o 2 peak ) (Lo) or 27 ± 2 min at 83 ± 2% V̇o 2 peak (Hi) in counterbalanced order. Preexercise muscle glycogen levels were not different between trials (Lo: 408 ± 35 mmol/kg dry mass Hi: 420 ± 43 mmol/kg dry mass) however, postexercise levels were lower ( P 0.05) in Hi (169 ± 18 mmol/kg dry mass) compared with Lo (262 ± 35 mmol/kg dry mass). Thus calculated muscle glycogen utilization was greater ( P 0.05) in Hi (251 ± 24 mmol/kg) than in Lo (146 ± 34). Exercise resulted in similar increases in GLUT4 gene expression in both trials. GLUT4 mRNA was increased immediately at the end of exercise (∼2-fold P 0.05) and remained elevated after 3 h of postexercise recovery. When measured 3 h after exercise, total crude membrane GLUT4 protein levels were 106% higher in Lo (3.3 ± 0.7 vs. 1.6 ± 0.3 arbitrary units) and 61% higher in Hi (2.9 ± 0.5 vs. 1.8 ± 0.5 arbitrary units) relative to preexercise levels. A main effect for exercise was observed, with no significant differences between trials. In conclusion, exercise at ∼40 and ∼80% V̇o 2 peak , with total work equal, increased GLUT4 mRNA and GLUT4 protein in human skeletal muscle to a similar extent, despite differences in exercise intensity and duration.
Publisher: Elsevier BV
Date: 06-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2014
Publisher: Springer Science and Business Media LLC
Date: 21-04-2023
DOI: 10.1007/S00394-023-03151-7
Abstract: Metabolomic dysregulation following a meal in overweight in iduals with the Metabolic Syndrome (MetS) involves multiple pathways of nutrient storage and oxidation. The aim of the current study was to perform an acute cross-over intervention to examine the interactive actions of meal glycaemic load (GL) on the dynamic responses of the plasma metabolome in overweight females. Postmenopausal women [63 ± 1.23y Healthy ( n = 20) and MetS ( n = 20)] ingested two differing high-carbohydrate test meals (73 g carbohydrate 51% energy) composed of either low glycemic index (LGI) or high (HGI) foods in a randomised sequence. Plasma metabolome was analysed using liquid chromatography–mass spectrometry (LC–MS). In the overweight women with MetS, there were suppressed postprandial responses for several amino acids (AAs), including phenylalanine, leucine, valine, and tryptophan, p 0.05 ), irrespective of the meal type. Meal GL exerted a limited impact on the overall metabolomic response, although the postprandial levels of alanine were higher with the low GL meal and uric acid was greater following the high GL meal ( p 0.05 ). MetS participants exhibited reduced differences in the concentrations of a small set of AAs and a limited group of metabolites implicated in energy metabolism following the meals. However, the manipulation of meal GL had minimal impact on the postprandial metabolome. This study suggests that the GL of a meal is not a major determinant of postprandial response, with a greater impact exerted by the metabolic health of the in idual. Trial registration Australia New Zealand Clinical Trials Registry: ACTRN12615001108505 (21/10/2015)
Publisher: Cold Spring Harbor Laboratory
Date: 13-09-2019
DOI: 10.1101/765495
Abstract: Muscle weakness and muscle wasting can be a consequence of aging (sarcopenia) and neuromuscular disorders (NMD). Genome-wide association (GWA) studies have identified genetic variants associated with grip strength (GS, an inverse measure of muscle weakness) and NMD (multiple sclerosis (MS), myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS)). However, how these variants contribute to the muscle weakness caused by aging or NMD remains obscure. We have integrated GS and NMD associated SNPs in a multimorbid analysis that leverages high-throughput chromatin interaction (Hi-C) data and expression quantitative trait loci (eQTL) data to identify allele-specific gene regulation ( i.e. eGenes). Pathways and shared drug targets that are enriched by colocalised eGenes were then identified using pathway and drug enrichment analysis. We identified gene regulatory mechanisms (eQTL-eGene effects) associated with GS, MG, MS and ALS. The eQTLs associated with GS regulate a subset of eGenes that are also regulated by the eQTLs of MS, MG and ALS. Yet, we did not find any eGenes commonly regulated by all four phenotypes associated eQTLs. By contrast, we identified three pathways (mTOR signaling, axon guidance, and alcoholism) that are commonly affected by the gene regulatory mechanisms associated with all four phenotypes. 13% of the eGenes we identified were known drug targets, and GS shares at least one druggable eGene and pathway with each of the NMD phenotypes. Collectively, these findings identify significant biological overlaps between GS and NMD, demonstrating the potential for spatial genetic analysis to identify mechanisms underlying muscle weakness due to aging and NMD.
Publisher: Informa UK Limited
Date: 03-01-2013
Publisher: Springer Science and Business Media LLC
Date: 31-01-2017
DOI: 10.1007/S10911-017-9375-X
Abstract: Human milk (HM) contains a complex array of hormones, including members of the glucocorticoid family. The predominant glucocorticoids, cortisol and cortisone may influence the growth and behaviour of the breastfed infant. However, little is understood of the factors regulating the levels of these hormones within HM. The aim of the study was to examine HM cortisol and cortisone concentration, measured in s les collected at each feed during a 24 hour period. Twenty three exclusively breastfeeding mothers collected milk, prior to and after each breastfeeding session over 24 hour period at 3.2(1.60) months. HM cortisol and cortisone levels were measured using high pressure liquid chromatography mass spectroscopy. Cortisone was the predominant glucocorticoid (3.40 ng/ml), and cortisol was detected in all s les (1.62 ng/ml). A positive correlation was found between cortisone and cortisol (r = 0.61, y = 1.93 ± 0.24, p < 0.0001). Cortisol and cortisone concentrations were significantly higher in feeds in the morning (2.97 ng/ml and 4.88 ng/ml), compared to afternoon (1.20 ng/ml and 3.54 ng/ml), evening (0.69 ng/ml and 2.13 ng/ml) and night (1.59 and 3.27 ng/ml). No difference was found between glucocorticoids level of the milk expressed for collection either before or immediately after the breastfeed, or between milk collected from the left or right breast. This study shows that HM glucocorticoid concentrations exhibit a 24 hour pattern, with highest peak levels in the early morning, reflecting the circadian pattern as previously reported in plasma. Thus, HM glucocorticoid concentrations are likely to reflect those in the maternal circulation.
Publisher: Wiley
Date: 17-06-2020
DOI: 10.1113/EP088744
Abstract: What is the central question of this study? Does short‐term high‐intensity interval training alter the composition of the microbiome and is this associated with exercise‐induced improvements in cardiorespiratory fitness and insulin sensitivity? What is the main finding and its importance? Although high‐intensity interval training increased insulin sensitivity and cardiovascular fitness, it did not alter the composition of the microbiome. This suggests that changes in the composition of the microbiome that occur with prolonged exercise training might be in response to changes in metabolic health rather than driving exercise training‐induced adaptations. Regular exercise reduces the risk of metabolic diseases, and the composition of the gut microbiome has been associated with metabolic function. We investigated whether short‐term high‐intensity interval training (HIIT) altered the ersity and composition of the bacterial community and whether there were associations with markers of insulin sensitivity or aerobic fitness. Cardiorespiratory fitness ( ) and body composition (dual energy X‐ray absorptiometry scan) were assessed and faecal and fasted blood s les collected from 14 lean (fat mass 21 ± 2%, aged 29 ± 2 years) and 15 overweight (fat mass 33 ± 2%, aged 31 ± 2 years) men before and after 3 weeks of HIIT training (8–12 × 60 s cycle ergometer bouts at power output interspersed by 75 s rest, three times per week). Gut microbiome composition was analysed by 16S rRNA gene licon sequencing. The HIIT significantly increased the aerobic fitness of both groups ( P 0.001) and improved markers of insulin sensitivity (lowered fasted insulin and HOMA‐IR P 0.001) in the overweight group. Despite differences in the abundance of several bacterial taxa being evident between the lean and overweight group, HIIT did not affect the overall bacterial ersity or community structure (α‐ ersity or β‐ ersity). No associations were found between the top 50 most abundant bacterial genera and cardiorespiratory fitness markers however, significant associations ( P 0.05) were observed between the abundance of the bacterial species Coprococcus _3, Blautia , Lachnospiraceae_ge and Dorea and insulin sensitivity markers in the overweight group. Our results suggest that short‐term HIIT does not greatly impact the overall composition of the gut microbiome, but that certain microbiome genera are associated with insulin sensitivity markers that were improved by HIIT in overweight participants.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2012
DOI: 10.1007/S00421-012-2458-X
Abstract: Older adults have an increase in circulating markers of inflammation. The current study examined whether there is an increase in the expression of inflammatory markers within the vastus lateralis, a major locomotive muscle, of older adults, and if so, whether the reduction in muscle strength and aerobic capacity in older adults is related to increased muscle inflammation. Skeletal muscle biopsies were taken from older adults (n = 17, 67 ± 1.6 years) and young in iduals (n = 16, 24 ± 0.6 years) under resting and fasting conditions. Muscle was analyzed for mRNA levels of intracellular inflammatory molecules (MCP1, TNFα and IL-1β) and total cellular protein abundance of cytokines, chemokines and kinases (IL-6, IL-8, MCP1, TNFα, p65 (NF-κB), JNK1/2 and STAT3). MCP1 expression was significantly higher (p < 0.05 50 %, mRNA and 40 %, protein) in elderly than younger participants, as was IL-8 (4 %). No detectable difference in kinase protein expression was observed for STAT3, JNK or p65 (NF-κB), TNFα or IL-6. Muscle strength was lower in the elderly compared to the young group (1.55 ± 0.17 vs. 2.56 ± 0.13 Nm/kg, p < 0.001). The elderly group also had a significantly lower VO(2peak) compared to the young group (24.9 ± 1.9 vs. 39.3 ± 1.9, p < 0.001), but muscle strength and VO(2peak) were not correlated with the examined inflammatory markers. Older adults have increased MCP1 (mRNA and protein abundance) and IL-8 (protein abundance) and also reduced muscle strength and VO(2peak). However, the reduction in muscle strength and VO(2peak) was not related to the increase in muscle inflammatory markers in this cohort.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.PLEFA.2017.12.003
Abstract: Arachidonic acid (ARA), an omega-6 polyunsaturated fatty acid (PUFA), is the metabolic precursor to the eicosanoid family of lipid mediators. Eicosanoids have potent pro-inflammatory actions, but also act as important autocrine aracrine signaling molecules in skeletal muscle growth and development. Whether dietary ARA is incorporated into skeletal muscle phospholipids and the resulting impact on intramuscular inflammatory and adaptive processes in-vivo is not known. In the current study, resistance trained men (≥1 year) received dietary supplementation with 1.5g/day ARA (n=9, 24 ± 1.5 years) or placebo (n=10, 26 ± 1.3 years) for 4-weeks while continuing their normal training regimen. Plasma and vastus lateralis muscle biopsies were collected in an overnight fasted state at baseline and week 4. ARA supplementation increased plasma content of ARA and gamma-linolenic acid, while decreasing relative abundance of linoleic acid, eicosapentaenoic acid, and dihomo-gamma-linolenic acid. In skeletal muscle, ARA and dihomo-gamma-linolenic acid content increased, whereas alpha-linolenic-acid was reduced. Compared to placebo, ARA supplementation reduced circulating platelet and monocyte number, and decreased the mRNA expression of the immune cell surface markers neutrophil elastase/CD66b and interleukin 1-beta, in peripheral blood mononuclear cells. In muscle, ARA supplementation increased mRNA expression of the myogenic regulatory factors MyoD and myogenin, but had no effect on a range of immune cell markers or inflammatory cytokines. These data show that dietary ARA supplementation can rapidly and safely modulate plasma and muscle fatty acid profile and promote myogenic gene expression in resistance trained men, without a risk of increasing basal systemic or intramuscular inflammation.
Publisher: American Physiological Society
Date: 15-11-2012
DOI: 10.1152/JAPPLPHYSIOL.01032.2011
Abstract: Aging is associated with reduced muscle mass, weakness, and increased fatigability. In skeletal muscle, the Na + -K + pump (NKA) is important in regulating Na + -K + gradients, membrane excitability, and thus contractility, but the effects of aging on muscle NKA are unclear. We investigated whether aging is linked with reduced muscle NKA by contrasting muscle NKA isoform gene expression and protein abundance, and NKA total content in 17 Elderly (66.8 ± 6.4 yr, mean ± SD) and 16 Young adults (23.9 ± 2.2 yr). Participants underwent peak oxygen consumption assessment and a vastus lateralis muscle biopsy, which was analyzed for NKA α 1 -, α 2 -, α 3 -, β 1 -, β 2 -, and β 3 -isoform gene expression (real-time RT-PCR), protein abundance (immunoblotting), and NKA total content ([ 3 H]ouabain binding sites). The Elderly had lower peak oxygen consumption (−36.7%, P = 0.000), strength (−36.3%, P = 0.001), NKA α 2 - (−24.4%, 11.9 ± 4.4 vs. 9.0 ± 2.7 arbitrary units, P = 0.049), and NKA β 3 -protein abundance (−23.0%, P = 0.041) than Young. The β 3 -mRNA was higher in Elderly compared with Young ( P = 0.011). No differences were observed between groups for other NKA isoform mRNA or protein abundance, or for [ 3 H]ouabain binding site content. Thus skeletal muscle in elderly in iduals was characterized by decreased NKA α 2 - and β 3 -protein abundance, but unchanged α 1 abundance and [ 3 H]ouabain binding. The latter was likely caused by reduced α 2 abundance with aging, preventing an otherwise higher [ 3 H]ouabain binding that might occur with a greater membrane density in smaller muscle fibers. Further study is required to verify reduced muscle NKA α 2 with aging and possible contributions to impaired exercise capability and daily living activities.
Publisher: Cambridge University Press (CUP)
Date: 29-10-2021
Publisher: MDPI AG
Date: 31-01-2020
DOI: 10.3390/NU12020380
Abstract: Cooking changes the texture and tenderness of red meat, which may influence its digestibility, circulatory amino acids (AA) and gastrointestinal (GI) hormonal responses in consumers. In a randomised crossover intervention, healthy males (n = 12) consumed a beef steak sandwich, in which the beef was cooked by either a pan-fried (PF) or sous-vide (SV) method. Plasma AA were measured by ultrahigh performance liquid chromatography (UPLC), while plasma GI hormones were measured using a flow cytometric multiplex array. Following meat ingestion, the circulatory concentrations of some of the essential AA (all the branched-chain AA: leucine, isoleucine and valine and threonine), some of the nonessential AA (glycine, alanine, tyrosine and proline) and some of the nonproteogenic AA (taurine, citrulline and ornithine) were increased from fasting levels by 120 or 180 min (p 0.05). There were no differences in circulating AA concentrations between cooking methods. Likewise, of the measured GI hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) concentrations increased from fasting levels after consumption of the steak sandwich (p 0.05), with no differences between the cooking methods. In the healthy male adults, protein digestion and circulating GI hormone responses to a beef-steak breakfast were unaltered by the different cooking methods.
Publisher: Wiley
Date: 03-1997
DOI: 10.1007/S11745-997-0039-7
Abstract: Recently it has been postulated that membrane fatty acid composition may be involved in the pathogenesis of insulin resistance and non-insulin dependent diabetes mellitus (NIDDM). The aim of this study was to determine whether alterations in tissue phospholipid (PL) fatty acids are present in hyperglycemic and hyperinsulinemic Psammomys obesus. On a native diet of salt bush, P. obesus (Israeli sand rat) remains lean and free of diabetes however, when placed on a normal laboratory chow, a significant proportion of these animals develops a number of metabolic disorders associated with NIDDM, providing an ideal animal model of obesity and NIDDM. Four groups of mature P. obesus were studied: group A: normoglycemic and normoinsulinemic group B: normoglycemic and hyperinsulinemic group C: hyperglycemic and hyperinsulinemic and group D: hyperglycemic and hypoinsulinemic. In liver and red gastrocnemius muscle, there were no significant differences between groups A, B, and C in fatty acid composition of PL. Minor differences in in idual fatty acids were demonstrated in group D animals (increased liver 20:4n-6 and increased muscle 22:5n-3) however, the unsaturation indices in liver and muscle were not significantly different between any of the groups. In considering that the minor changes in group D animals were not demonstrated in hyperinsulinemic group B animals or hyperglycemic, hyperinsulinemic group C animals, it is likely that the differences in group D animals were secondary to the more severe disturbances in glucose homeostasis and hypoinsulinemia present in these animals. The results of this study suggest that in this rodent diabetic model significant disturbances in glucose homeostasis and hyperinsulinemia may develop independently of changes in tissue fatty acid composition.
Publisher: Frontiers Media SA
Date: 13-01-2021
Abstract: Faecal proteomics targeting biomarkers of immunity and inflammation have demonstrated clinical application for the identification of changes in gastrointestinal function. However, there are limited comprehensive analyses of the host faecal proteome and how it may be influenced by dietary factors. To examine this, the Homo sapiens post-diet proteome of older males was analysed at the completion of a 10-week dietary intervention, either meeting the minimum dietary protein recommendations (RDA n = 9) or twice the recommended dietary allowance (2RDA, n = 10). The host faecal proteome differed markedly between in iduals, with only a small subset of proteins present in ≥ 60% of subjects (14 and 44 proteins, RDA and 2RDA, respectively, with only 7 common to both groups). No differences were observed between the diet groups on the profiles of host faecal proteins. Faecal proteins were detected from a wide range of protein classes, with high inter-in idual variation and absence of obvious impact in response to diets with markedly different protein intake. This suggests that well-matched whole food diets with two-fold variation in protein intake maintained for 10 weeks have minimal impact on human faecal host proteins.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.EXGER.2018.05.006
Abstract: A gradual loss of skeletal muscle mass is a common feature of aging, leading to impaired insulin sensitivity and mobility. Sestrin1, 2, 3 are multifunctional proteins that regulate the mammalian target of rapamycin complex (mTORC1), autophagy and redox homeostasis. It is unclear how aging affects Sestrins and their downstream targets in human, therefore this study examined the basal expression of Sestrins in three age groups, young, middle-aged and older men and explored the mTORC1 pathway, autophagy markers and antioxidant regulation. Older men had less Sestrin1 and 3 protein and a different pattern of Sestrin2 electrophoretic mobility. The mRNA expression of SESN1 was upregulated in older men, but the discrepancy was not by microRNA expression. Although protein expressions of Sestrins were downregulated with aging, phosphorylation of AMP-dependent protein kinase (AMPKα
Publisher: Elsevier BV
Date: 02-1998
DOI: 10.1016/S0026-0495(98)90211-6
Abstract: High circulating fasting and prandial triglyceride levels are associated with both insulin resistance and the development of cardiovascular disease. The aim of this investigation was to study the effects of NO-1886, a novel lipoprotein lipase (LPL) activator, on triglyceride levels, fat oxidation, and glucose tolerance in fructose-fed rats, a hypertriglyceridemic model of insulin resistance. Adult male Wistar rats were fed for 4 weeks with a high-starch diet or a high-fructose diet without and with NO-1886 (50 mg x kg[-1] x d[-1] orally). Fructose feeding increased plasma triglyceride levels, an effect that was ameliorated by NO-1886 treatment (week 1/week 4: starch-fed, 2.4 +/- 0.1/2.8 +/- 0.2 mmol/L fructose-fed, 3.6 +/- 0.5/5.5 +/- 0.5 fructose + NO-1886, 2.7 +/- 0.2/3.6 +/- 0.3). The mean 24-hour respiratory quotient (RQ) was significantly lower in the fructose + NO-1886 group compared with fructose-fed rats, indicating increased oxidation of fat. Fructose feeding elevated liver triglyceride levels by 74% (P < .01), an effect not altered by NO-1886. Red and white quadriceps hindlimb muscle triglyceride levels were not different between groups. Glucose tolerance (intravenous test in long-term cannulated rats) was mildly deteriorated and fasting insulin and glucose levels were elevated in fructose-fed rats, effects which were ameliorated by NO-1886. In conclusion, in the fructose-fed rat model of hypertriglyceridemia and insulin resistance, addition of a LPL activator reduced circulating triglyceride levels without causing increased muscle triglyceride accumulation or deterioration in glucose tolerance. LPL activators may prove to be a fruitful avenue to explore in the search for new therapeutic agents in the treatment of dyslipidemias and insulin resistance.
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.NUTRES.2009.10.003
Abstract: The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-alpha, CPT-1, ACO) however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-beta, and PPAR-gamma) and BT (C/EBP-beta), while decreasing LPL, HSL, and UCP-2 expression EGCG increased expression of UCP-2 and PPAR-gamma genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention.
Publisher: American Physiological Society
Date: 15-11-2013
DOI: 10.1152/JAPPLPHYSIOL.00789.2013
Abstract: Knee osteoarthritis (OA) is a debilitating disorder prevalent in older populations that is accompanied by declines in muscle mass, strength, and physical activity. In skeletal muscle, the Na + -K + pump (NKA) is pivotal in ion homeostasis and excitability and is modulated by disuse and exercise training. This study examined the effects of OA and aging on muscle NKA in 36 older adults (range 55–81 yr), including 19 with OA (69.9 ± 6.5 yr, mean ± SD) and 17 asymptomatic controls (CON, 66.8 ± 6.4 yr). Participants completed knee extensor strength testing and a physical activity questionnaire. A vastus lateralis muscle biopsy was analyzed for NKA content ([ 3 H]ouabain binding sites), α 1–3 - and β 1–3 -isoform protein abundance (immunoblotting), and mRNA (real-time RT-PCR). The association between age and NKA content was investigated within the OA and CON groups and in pooled data. The NKA content was also contrasted between subgroups below and above the median age of 68.5 yr. OA had lower strength (−40.8%, P = 0.005), but higher NKA α 2 - (∼34%, P = 0.006) and α 3 -protein (100%, P = 0.016) abundance than CON and performed more incidental physical activity ( P = 0.035). No differences were found between groups for NKA content, abundance of other NKA isoforms, or gene expression. There was a negative correlation between age and NKA content within OA ( r = −0.63, P = 0.03) and with both groups combined ( r = −0.47, P = 0.038). The NKA content was 25.5% lower in the older (69–81 yr) than in the younger (55–68 yr) subgroup. Hence older age, but not knee OA, was related to lowered muscle NKA content in older adults.
Publisher: Wiley
Date: 12-04-2006
Publisher: Wiley
Date: 08-2014
DOI: 10.14814/PHY2.12112
Publisher: American Physiological Society
Date: 10-2014
DOI: 10.1152/AJPENDO.00276.2014
Abstract: This study investigated the effects of high-intensity interval training (HIIT) vs. work-matched moderate-intensity continuous exercise (MOD) on metabolism and counterregulatory stress hormones. In a randomized and counterbalanced order, 10 well-trained male cyclists and triathletes completed a HIIT session [81.6 ± 3.7% maximum oxygen consumption (V̇o 2 max ) 72.0 ± 3.2% peak power output 792 ± 95 kJ] and a MOD session (66.7 ± 3.5% V̇o 2 max 48.5 ± 3.1% peak power output 797 ± 95 kJ). Blood s les were collected before, immediately after, and 1 and 2 h postexercise. Carbohydrate oxidation was higher ( P = 0.037 20%), whereas fat oxidation was lower ( P = 0.037 −47%) during HIIT vs. MOD. Immediately after exercise, plasma glucose ( P = 0.024 20%) and lactate ( P 0.01 5.4×) were higher in HIIT vs. MOD, whereas total serum free fatty acid concentration was not significantly different ( P = 0.33). Targeted gas chromatography-mass spectromtery metabolomics analysis identified and quantified 49 metabolites in plasma, among which 11 changed after both HIIT and MOD, 13 changed only after HIIT, and 5 changed only after MOD. Notable changes included substantial increases in tricarboxylic acid intermediates and monounsaturated fatty acids after HIIT and marked decreases in amino acids during recovery from both trials. Plasma adrenocorticotrophic hormone ( P = 0.019), cortisol ( P 0.01), and growth hormone ( P 0.01) were all higher immediately after HIIT. Plasma norepinephrine ( P = 0.11) and interleukin-6 ( P = 0.20) immediately after exercise were not significantly different between trials. Plasma insulin decreased during recovery from both HIIT and MOD ( P 0.01). These data indicate distinct differences in specific metabolites and counterregulatory hormones following HIIT vs. MOD and highlight the value of targeted metabolomic analysis to provide more detailed insights into the metabolic demands of exercise.
Publisher: SAGE Publications
Date: 13-09-2018
Abstract: Preterm birth is a stressful event for both the mother and infant. Whereas the initiation of breastfeeding is important for preterm infant health, little is known of the glucocorticoid hormones (cortisol and cortisone) in human milk following preterm birth. The aim of this study was to investigate the relationship between human milk glucocorticoid concentrations and preterm birth. Human milk was s led weekly for up to 6 weeks from 22 women who delivered a preterm infant at 28 to 32 weeks’ gestation. Human milk was analyzed for total and free cortisol and cortisone concentrations using liquid chromatography-tandem mass spectrometry. Milk s led from mothers of preterm infants had more cortisone than cortisol ( p .001), with a strong correlation between both hormones ( p = .001, r = .85). The cortisone was significantly higher in the milk of mothers who delivered infants after 30 weeks compared with those who delivered before 30 weeks of gestation ( p = .02). Glucocorticoid concentrations did not change over the s ling time (weeks 1 to 6 postpartum) and did not differ by infant gender. Glucocorticoids were present in all milk s les following preterm birth. Cortisone concentration tended to be higher in those who delivered after 30 weeks’ gestation but did not increase further over the weeks following birth.
Publisher: American Physiological Society
Date: 15-02-2015
Publisher: Proceedings of the National Academy of Sciences
Date: 06-05-2008
Abstract: In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE −/− ) and compared with wild-type littermates. Compared with wild-type littermates, ACE −/− mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE −/− mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE −/− mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excreted in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE −/− mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.
Publisher: American Dairy Science Association
Date: 05-2015
Abstract: Bovine milk contains biologically active peptides that may modulate growth and development within humans. In this study, targeted bovine-derived proteins were evaluated for their effects on signal transducer and activator of transcription-3 (STAT3) phosphorylation in human skeletal muscle cells. Following an acute exposure, bovine-derived acidic fibroblast growth factor-1 (FGF) and leukemia inhibitory factor (LIF) activated STAT3 in differentiating myotubes. Chronic exposure to FGF and LIF during the proliferative phase reduced myoblast proliferation and elevated MyoD and creatine kinase (CKM) mRNA expression without altering apoptotic genes. In mature myotubes, neither FGF nor LIF elicited any action. Together, these data indicate that a reduction in proliferation in the presence of bovine-derived FGF or LIF may stimulate early maturation of myoblasts.
Publisher: Wiley
Date: 28-04-2011
DOI: 10.1002/ART.30287
Abstract: Increased inflammation and pain are inseparable parts of knee osteoarthritis (OA) that may lead to disuse of the affected limb. The aim of this study was to examine the effects of knee OA on inflammation- and atrophy-related genes and proteins in the vastus lateralis muscle of patients with knee OA. Nineteen patients with knee OA and 14 asymptomatic control subjects matched for age and body mass index underwent strength measurements and a muscle biopsy. Muscle was analyzed for the total cellular protein of inflammatory kinases (p65 NF-κB, JNK1/2, STAT-3, and suppressor of cytokine signaling 3 [SOCS-3]) and inflammatory intracellular molecules (interleukin-6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1], tumor necrosis factor α [TNFα], IL-1β, and atrogin-1). Knee OA resulted in greater levels of IL-6 protein (34% P = 0.002). The levels of inflammatory kinases, including STAT-3 (187% P = 0.002), p65 NF-κB (156% P = 0.002), and JNK1 (179% P = 0.027), were also elevated. Furthermore, elevated expression of gene transcripts encoding MCP-1 (28% P = 0.023), TNFα (85% P < 0.001), and SOCS-3 (38% P = 0.055) was observed in patients with knee OA compared with control subjects. Patients with knee OA had reduced muscle strength compared with control subjects (mean ± SEM 84.7 ± 8.7 versus 143.1 ± 20.8 Nm P = 0.005). Negative correlations were observed between muscle strength and MCP-1 protein abundance (r = -0.37 [P = 0.042]) and the gene expression of TNFα and atrogin-1 messenger RNA (r = -0.46 [P = 0.012] and r = -0.36 [P = 0.040], respectively). Gene expression and the protein abundance of numerous muscle markers of inflammation and atrophy were elevated in patients with knee OA, and the increase in muscle inflammation was associated with a reduction in muscle strength. Given the role inflammation markers may play in muscle strength and atrophy, further studies are needed to investigate the effect of exercise intervention on skeletal muscle inflammation.
Publisher: Springer Science and Business Media LLC
Date: 27-06-2014
DOI: 10.1007/S00421-014-2936-4
Abstract: Intense resistance exercise causes mechanical loading of skeletal muscle, followed by muscle adaptation. Chemotactic factors likely play an important role in these processes. We investigated the time course of changes in the expression and tissue localization of several key chemotactic factors in skeletal muscle during the early phase of recovery following resistance exercise. Muscle biopsy s les were obtained from vastus lateralis of eight untrained men (22 ± 0.5 years) before and 2, 4 and 24 h after three sets of leg press, squat and leg extension at 80 % 1-RM. Monocyte chemotactic protein-1 (95×), interleukin-8 (2,300×), IL-6 (317×), urokinase-type plasminogen activator (15×), vascular endothelial growth factor (2×) and fractalkine (2.5×) mRNA was significantly elevated 2 h post-exercise. Interleukin-8 (38×) and interleukin-6 (58×) protein was also significantly elevated 2 h post-exercise, while monocyte chemotactic protein-1 protein was significantly elevated at 2 h (22×) and 4 h (21×) post-exercise. Monocyte chemotactic protein-1 and interleukin-8 were expressed by cells residing in the interstitial space between muscle fibers and, in some cases, were co-localized with CD68 + macrophages, PAX7 + satellite cells and blood vessels. However, the patterns of staining were inconclusive and not consistent. In conclusion, resistance exercise stimulated a marked increase in the mRNA and protein expression of various chemotactic factors in skeletal muscle. Myofibers were not the dominant source of these factors. These findings suggest that chemotactic factors regulate remodeling/adaptation of skeletal muscle during the early phase of recovery following resistance exercise.
Publisher: Frontiers Media SA
Date: 29-07-2020
Publisher: Springer Science and Business Media LLC
Date: 14-02-2018
DOI: 10.1007/S00394-018-1620-6
Abstract: Elemental deficiencies are highly prevalent and have a significant impact on health. However, clinical monitoring of plasma elemental responses to foods remains largely unexplored. Data from in vitro studies show that red meat (beef) is a highly bioavailable source of several key elements, but cooking method may influence this bioavailability. We therefore studied the postprandial responses to beef steak, and the effects of two different cooking methods, in healthy young males. In a randomized cross-over controlled trial, healthy males (n = 12, 18-25 years) were fed a breakfast of beef steak (270 ± 20 g) in which the meat was either pan-fried (PF) or sous-vide (SV) cooked. Baseline and postprandial blood s les were collected and the plasma concentrations of 15 elements measured by inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations of Fe and Zn changed after meal ingestion, with plasma Fe increasing (p < 0.001) and plasma Zn decreasing (p < 0.05) in response to both cooking methods. The only potential treatment effect was seen for Zn, where the postprandial area under the curve was lower in response to the SV meal (2965 ± 357) compared to the PF meal (3190 ± 310 p < 0.05). This multi-element approach demonstrated postprandial responsiveness to a steak meal, and an effect of the cooking method used. This suggests the method would provide insight in future elemental metabolic studies to evaluate responses to meat-based meals, including longer-term interventions in more specifically defined cohorts to clearly establish the role of red meat as an important source of elements.
Publisher: American Physiological Society
Date: 08-07-2004
DOI: 10.1152/PHYSIOLGENOMICS.00067.2004
Abstract: Studies examining gene expression with RT-PCR typically normalize their mRNA data to a constitutively expressed housekeeping gene. The validity of a particular housekeeping gene must be determined for each experimental intervention. We examined the expression of various housekeeping genes following an acute bout of endurance (END) or resistance (RES) exercise. Twenty-four healthy subjects performed either a interval-type cycle ergometry workout to exhaustion (∼75 min END) or 300 single-leg eccentric contractions (RES). Muscle biopsies were taken before exercise and 3 h and 48 h following exercise. Real-time RT-PCR was performed on β-actin, cyclophilin (CYC), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and β2-microglobulin (β2M). In a second study, 10 healthy subjects performed 90 min of cycle ergometry at ∼65% of V̇o 2 max , and we examined a fifth housekeeping gene, 28S rRNA, and reexamined β2M, from muscle biopsy s les taken immediately postexercise. We showed that CYC increased 48 h following both END and RES exercise (3- and 5-fold, respectively P 0.01), and 28S rRNA increased immediately following END exercise (2-fold P = 0.02). β-Actin trended toward an increase following END exercise (1.85-fold collapsed across time P = 0.13), and GAPDH trended toward a small yet robust increase at 3 h following RES exercise (1.4-fold P = 0.067). In contrast, β2M was not altered at any time point postexercise. We conclude that β2M and β-actin are the most stably expressed housekeeping genes in skeletal muscle following RES exercise, whereas β2M and GAPDH are the most stably expressed following END exercise.
Publisher: The Endocrine Society
Date: 12-02-2022
Abstract: The kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth. In this prospective longitudinal study, we investigate the relationship between cord blood kynurenine metabolites and measures of adiposity from birth to 4.5 years. Liquid chromatography–tandem mass spectrometry was used to quantify cord blood kynurenine metabolites in 812 neonates from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Fat percentage was measured by air displacement plethysmography and abdominal adipose tissue compartment volumes superficial (sSAT) and deep subcutaneous (dSAT) and internal adipose tissue were quantified by magnetic resonance imaging at early infancy in a smaller subset of neonates, and again at 4 to 4.5 years of age. Cord blood kynurenine metabolites appeared to be higher in female newborns, higher in Indian newborns compared with Chinese newborns, and higher in infants born by cesarean section compared with vaginal delivery. Kynurenine, xanthurenic acid, and quinolinic acid were positively associated with birthweight, but not with subsequent weight during infancy and childhood. Quinolinic acid was positively associated with sSAT at birth. Kynurenic acid and quinolinic acid were positively associated with fat percentage at 4 years. Several cord blood kynurenine metabolite concentrations were positively associated with birthweight, with higher kynurenic acid and quinolinic acid correlating to higher percentage body fat in childhood, suggesting these cord blood metabolites as biomarkers of early childhood adiposity.
Publisher: Elsevier BV
Date: 2002
Publisher: Wiley
Date: 09-1997
Publisher: Elsevier BV
Date: 07-2010
Publisher: Wiley
Date: 26-07-2016
Publisher: Wiley
Date: 08-2022
DOI: 10.1113/JP283017
Abstract: We investigated whether digoxin lowered muscle Na + ,K + ‐ATPase (NKA), impaired muscle performance and exacerbated exercise K + disturbances. Ten healthy adults ingested digoxin (0.25 mg DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105% peak‐workrate , 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% and 67% , 90% to fatigue) trials using a double‐blind, crossover, randomised, counter‐balanced design. Arterial (a) and antecubital venous (v) blood was s led (FF, LC) and muscle biopsied (LC, rest, 67% , fatigue, 3 h after exercise). In DIG, in resting muscle, [ 3 H]‐ouabain binding site content (OB‐F ab ) was unchanged however, bound‐digoxin removal with Digibind revealed total ouabain binding (OB+F ab ) increased (8.2%, P = 0.047), indicating 7.6% NKA–digoxin occupancy. Quadriceps muscle strength declined in DIG (−4.3%, P = 0.010) but fatiguability was unchanged. During LC, in DIG (main effects), time to fatigue and [K + ] a were unchanged, whilst [K + ] v was lower ( P = 0.042) and [K + ] a‐v greater ( P = 0.004) than in CON with exercise (main effects), muscle OB‐F ab was increased at 67% (per wet‐weight, P = 0.005 per protein P = 0.001) and at fatigue (per protein, P = 0.003), whilst [K + ] a , [K + ] v and [K + ] a‐v were each increased at fatigue ( P = 0.001). During FF, in DIG (main effects), time to fatigue, [K + ] a , [K + ] v and [K + ] a‐v were unchanged with exercise (main effects), plasma [K + ] a , [K + ] v , [K + ] a‐v and muscle K + efflux were all increased at fatigue ( P = 0.001). Thus, muscle strength declined, but functional muscle NKA content was preserved during DIG, despite elevated plasma digoxin and muscle NKA–digoxin occupancy, with K + disturbances and fatiguability unchanged. image The Na + ,K + ‐ATPase (NKA) is vital in regulating skeletal muscle extracellular potassium concentration ([K + ]), excitability and plasma [K + ] and thereby also in modulating fatigue during intense contractions. NKA is inhibited by digoxin, which in cardiac patients lowers muscle functional NKA content ([ 3 H]‐ouabain binding) and exacerbates K + disturbances during exercise. In healthy adults, we found that digoxin at clinical levels surprisingly did not reduce functional muscle NKA content, whilst digoxin removal by Digibind antibody revealed an ∼8% increased muscle total NKA content. Accordingly, digoxin did not exacerbate arterial plasma [K + ] disturbances or worsen fatigue during intense exercise, although quadriceps muscle strength was reduced. Thus, digoxin treatment in healthy participants elevated serum digoxin, but muscle functional NKA content was preserved, whilst K + disturbances and fatigue with intense exercise were unchanged. This resilience to digoxin NKA inhibition is consistent with the importance of NKA in preserving K + regulation and muscle function.
Publisher: American Physiological Society
Date: 04-2007
DOI: 10.1152/JAPPLPHYSIOL.00821.2006
Abstract: The purpose of the present study was to determine in human skeletal muscle whether a single exercise bout and 7 days of consecutive endurance (cycling) training 1) increased insulin-stimulated Akt pSer 473 and 2) altered the abundance of the protein tyrosine phosphatases (PTPases), PTP1B and SHP2. In healthy, untrained men ( n = 8 24 ± 1 yr), glucose infusion rate during a hyperinsulinemic euglycemic cl , when compared with untrained values, was not improved 24 h following a single 60-min bout of endurance cycling but was significantly increased (∼30% P 0.05) 24 h following completion of 7 days of exercise training. Insulin-stimulated Akt pSer 473 was ∼50% higher ( P 0.05) 24 h following the acute bout of exercise, with this effect remaining after 7 days of training ( P 0.05). Insulin-stimulated insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation were not altered 24 h after acute exercise and short-term training. Insulin did not acutely regulate the localization of the PTPases, PTP1B or SHP2, although cytosolic protein abundance of SHP2 was increased ( P 0.05 main effect) 24 h following acute exercise and short-term training. In conclusion, insulin-sensitive Akt pSer 473 and cytosolic SHP2 protein abundance are higher after acute exercise and short-term training, and this effect appears largely due to the residual effects of the last bout of prior exercise. The significance of exercise-induced alterations in cytosolic SHP2 and insulin-stimulated Akt pSer 473 on the improvement in insulin sensitivity requires further elucidation.
Publisher: Oxford University Press (OUP)
Date: 10-07-2008
DOI: 10.1634/STEMCELLS.2008-0325
Abstract: Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-γ (PPARγ) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPARγ agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation. Disclosure of potential conflicts of interest is found at the end of this article.
Publisher: Frontiers Media SA
Date: 25-09-2018
Publisher: Georg Thieme Verlag KG
Date: 27-02-2014
Abstract: Exercise elicits skeletal-muscle adaptations which are important for improved health outcomes. We compared the effects of a futsal game (FUT) and moderate-intensity continuous exercise (MOD), on the skeletal-muscle protein signalling responses in young, healthy in iduals. 16 men undertook an incremental exercise test and a resting muscle biopsy performed >48 h apart. They were then randomly allocated to either FUT (n=12) consisting of 2 x 20 min halves, or MOD (n=8) consisting of a work-matched running bout performed at an intensity corresponding to the in idual ventilatory threshold 1. Work matching was achieved by means of triaxial accelerometers. Immediately after FUT and MOD, participants underwent a second biopsy to assess exercise-induced changes in protein signalling. Total and phosphorylated protein abundance was assessed via western blotting. Both FUT and MOD altered signalling responses in skeletal muscle. FUT increased total ATF2 protein abundance (p=0.048) and phosphorylation (p=0.029), while no changes occurred with MOD. Both exercise regimes increased ACC phosphorylation (p=0.01) and returned a trend for increased p38MAPK phosphorylation. Futsal may be employed as an alternative to continuous exercise to elicit muscle adaptations which may be associated with improved health outcomes. As only FUT increased ATF2 activation, this protein might be a target of future investigation on exercise-induced signalling.
Publisher: American Physiological Society
Date: 04-2007
DOI: 10.1152/JAPPLPHYSIOL.01147.2006
Abstract: The transcription factor signal transducer and activator of transcription 3 (STAT3) has been identified as a mediator of cytokine signaling and implicated in hypertrophy however, the importance of this pathway following resistance exercise in human skeletal muscle has not been investigated. In the present study, the phosphorylation and nuclear localization of STAT3, together with STAT3-regulated genes, were measured in the early recovery period following intense resistance exercise. Muscle biopsy s les from healthy subjects (7 males, 23.0 + 0.9 yr) were harvested before and again at 2, 4, and 24 h into recovery following a single bout of maximal leg extension exercise (3 sets, 12 repetitions). Rapid and transient activation of phosphorylated (tyrosine 705) STAT3 was observed at 2 h postexercise. STAT3 phosphorylation paralleled the transient localization of STAT3 to the nucleus, which also peaked at 2 h postexercise. Downstream transcriptional events regulated by STAT3 activation peaked at 2 h postexercise, including early responsive genes c-FOS (800-fold), JUNB (38-fold), and c-MYC (140-fold) at 2 h postexercise. A delayed peak in VEGF (4-fold) was measured 4 h postexercise. Finally, genes associated with modulating STAT3 signaling were also increased following exercise, including the negative regulator SOCS3 (60-fold). Thus, following a single bout of intense resistance exercise, a rapid phosphorylation and nuclear translocation of STAT3 are evident in human skeletal muscle. These data suggest that STAT3 signaling is an important common element and may contribute to the remodeling and adaptation of skeletal muscle following resistance exercise.
Publisher: Springer Science and Business Media LLC
Date: 2000
Abstract: To compare the frequency and duration of varying intensities of physical activity performed by adults trying to lose weight, avoid gaining weight and not actively trying to control their weight, and to compare these groups' beliefs about the physical activity they should perform. Random postal survey of 2500 Victorian adults selected from the Australian electoral roll (response rate=42%). One-week physical activity recall (frequency and duration of walking, other moderate activity and vigorous activity), BMI (based on self-reported height and weight) and weight-control behaviour. At the time of the survey, 27% of respondents were actively trying to avoid gaining weight, 23. 9% trying to lose weight and 49.1% undertaking no weight control. Respondents spent a mean time of 4.0 (+/-7.1) h walking, 5.5 (+/-7. 9) h in moderate activity and 3.1(+/-5.9) h in vigorous activity during the week prior to the survey. Women trying to lose weight or avoid gaining weight engaged in vigorous activity more often than women not trying to control their weight. After adjusting for age, education and BMI, women trying to avoid gaining weight were 2.4 times more likely, and women trying to lose weight 2.5 times more likely, to have met current physical activity guidelines than women undertaking no weight control. On average, respondents believed they should spend 5.2 (+/-6.9) h walking, 6.5 (+/-8.2) h in moderate activity and 4.3 (+/-6.5) h in vigorous activity each week. Women trying to lose weight felt they should perform vigorous activity more often than other women. Weight-control behaviour was not associated with physical activity beliefs and behaviours of men. Walking is a common activity among adults attempting weight control. However, many men and women do not fully recognize the value of moderate-intensity physical activity. Future efforts should be directed at promoting the role of moderate-intensity activity in weight control, particularly activity that can be performed outside of planned activity sessions. International Journal of Obesity (2000)24, 81-87
Publisher: American Physiological Society
Date: 08-2018
DOI: 10.1152/JAPPLPHYSIOL.00169.2018
Abstract: Strenuous exercise can result in skeletal muscle damage, leading to the systemic mobilization, activation, and intramuscular accumulation of blood leukocytes. Eicosanoid metabolites of arachidonic acid (ARA) are potent inflammatory mediators, but whether changes in dietary ARA intake influence exercise-induced inflammation is not known. This study investigated the effect of 4 wk of dietary supplementation with 1.5 g/day ARA ( n = 9, 24 ± 1.5 yr) or corn-soy oil placebo ( n = 10, 26 ± 1.3 yr) on systemic and intramuscular inflammatory responses to an acute bout of resistance exercise (8 sets each of leg press and extension at 80% one-repetition maximum) in previously trained men. Whole EDTA blood, serum, peripheral blood mononuclear cells (PMBCs), and skeletal muscle biopsies were collected before exercise, immediately postexercise, and at 2, 4, and 48 h of recovery. ARA supplementation resulted in higher exercise-stimulated serum creatine kinase activity [incremental area under the curve (iAUC) P = 0.046] and blood leukocyte counts (iAUC for total white cells, P 0.001 neutrophils: P = 0.007 monocytes: P = 0.015). The exercise-induced fold change in peripheral blood mononuclear cell mRNA expression of interleukin-1β ( IL1B), CD11b ( ITGAM), and neutrophil elastase ( ELANE), as well as muscle mRNA expression of the chemokines interleukin-8 ( CXCL8) and monocyte chemoattractant protein 1 ( CCL2) was also greater in the ARA group than placebo. Despite this, ARA supplementation did not influence the histological presence of leukocytes within muscle, perceived muscle soreness, or the extent and duration of muscle force loss. These data show that ARA supplementation transiently increased the inflammatory response to acute resistance exercise but did not impair recovery. NEW & NOTEWORTHY Daily arachidonic acid supplementation for 4 wk in trained men augmented the acute systemic and intramuscular inflammatory response to a subsequent bout of resistance exercise. Greater exercise-induced inflammatory responses in men receiving arachidonic acid supplementation were not accompanied by increased symptoms of exercise-induced muscle damage. Although increased dietary arachidonic acid intake does not appear to influence basal inflammation in humans, the acute inflammatory response to exercise stress is transiently increased following arachidonic acid supplementation.
Publisher: AMPCo
Date: 06-2012
DOI: 10.5694/MJA12.10372
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/464921
Abstract: Marine omega-3 rich oils are used by more than a third of American adults for a wide range of purported benefits including prevention of cardiovascular disease. These oils are highly prone to oxidation to lipid peroxides and other secondary oxidation products. Oxidized oils may have altered biological activity making them ineffective or harmful, though there is also evidence that some beneficial effects of marine oils could be mediated through lipid peroxides. To date, human clinical trials have not reported the oxidative status of the trial oil. This makes it impossible to understand the importance of oxidation to efficacy or harm. However, animal studies show that oxidized lipid products can cause harm. Oxidation of trial oils may be responsible for the conflicting omega-3 trial literature, including the prevention of cardiovascular disease. The oxidative state of an oil can be simply determined by the peroxide value and anisidine value assays. We recommend that all clinical trials investigating omega-3 harms or benefits report the results of these assays this will enable better understanding of the benefits and harms of omega-3 and the clinical importance of oxidized supplements.
Publisher: Wiley
Date: 10-2014
DOI: 10.14814/PHY2.12172
Publisher: Springer Science and Business Media LLC
Date: 22-12-2007
DOI: 10.1007/S00421-006-0376-5
Abstract: Endurance exercise transiently increases the mRNA of key regulatory proteins involved in skeletal muscle metabolism. During prolonged exercise and subsequent recovery, circulating plasma fatty acid (FA) concentrations are elevated. The present study therefore aimed to determine the sensitivity of key metabolic genes to FA exposure, assessed in vitro using L6 myocytes and secondly, to measure the expression of these same set of genes in vivo, following a single exercise bout when the post-exercise rise in plasma FA is abolished by acipimox. Initial studies using L6 myotubes demonstrated dose responsive sensitivity for both PDK4 and PGC-1alpha mRNA to acute FA exposure in vitro. Nine active males performed two trials consisting of 2 h exercise, followed by 2 h of recovery. In one trial, plasma FA availability was reduced by the administration of acipimox (LFA), a pharmacological inhibitor of adipose tissue lipolysis, and in the second trial a placebo was provided (CON). During the exercise bout and during recovery, the rise in plasma FA and glycerol was abolished by acipimox treatment. Following exercise the mRNA abundance of PDK4 and PGC-1alpha were elevated and unaffected by either acipimox or placebo. Further analysis of skeletal muscle gene expression demonstrated that the CPT I gene was suppressed in both trials, whilst UCP-3 gene was only modestly regulated by exercise alone. Acipimox ingestion did not alter the response for both CPT I and UCP-3. Thus, this study demonstrates that the normal increase in circulating concentrations of FA during the later stages of exercise and subsequent recovery is not required to induce skeletal muscle mRNA expression of several proteins involved in regulating substrate metabolism.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2018
DOI: 10.1007/S00421-018-3853-8
Abstract: Dietary protein and resistance exercise (RE) are both potent stimuli of the mammalian target of rapamycin complex 1 (mTORC1). Sestrins1, 2, 3 are multifunctional proteins that regulate mTORC1, stimulate autophagy and alleviate oxidative stress. Of this family, Sestrin2 is a putative leucine sensor implicated in mTORC1 and AMP-dependent protein kinase (AMPK) regulation. There is currently no data examining the responsiveness of Sestrin2 to dietary protein ingestion, with or without RE. In Study 1, 16 males ingested either 10 or 20 g of milk protein concentrate (MPC) with muscle biopsies collected pre, 90 and 210 min post-beverage consumption. In Study 2, 20 males performed a bout of RE immediately followed by the consumption of 9 g of MPC or carbohydrate placebo. Analysis of Sestrins, AMPK and antioxidant responses was examined. Dietary protein ingestion did not result in Sestrin2 mobility shift. After RE, Sestrin2 phosphorylation state was significantly altered and was not further modified by post-exercise protein or carbohydrate ingestion. With RE, AMPK phosphorylation remained stable, while the mRNA expressions of several antioxidants were upregulated. Dietary protein ingestion did not affect the signalling by the family of Sestrins. With RE, Sestrin2 was hyperphosphorylated, with no further evidence of a relationship to AMPK signalling.
Publisher: Frontiers Media SA
Date: 28-05-2021
Abstract: Background: Differing environmental conditions experienced by mother-infant dyads may influence composition of the milk received by the infant. As a consequence, erse milk compositional profiles may contribute to different postnatal outcomes, especially in infants facing adverse perinatal environments. We investigated whether variability in milk concentrations of key metabolic hormones is associated with different growth outcomes in infants born preterm, a perinatal complication known to impact on infant growth. Methods: Human milk s les were collected from 169 mothers of 191 infants enrolled in the DIAMOND trial, a randomized trial of nutrition for moderate-late preterm infants, at 5 and 10 days postpartum and again at 4 months' corrected age and analyzed for leptin, adiponectin and insulin-like growth factor (IGF)-1. Infant weight and body composition were measured at birth, discharge and 4 months' corrected age. Multiple linear regression models were used to examine correlations between milk hormone concentrations, weight z-scores and body composition at discharge and 4 months' corrected age, and weight gain from birth to 4 months' corrected age. Sex-specific interactions were examined. Results: Higher milk IGF-1 concentrations on day 5 after birth were associated with greater infant fat-free mass at 4 months' corrected age. Milk IGF-1 concentrations at 4 months were positively associated with fat mass and fat-free mass at 4 months in boys but not girls. Milk leptin concentrations on day 5 after birth were positively associated with fat mass at discharge from hospital, but negatively associated with fat mass at 4 months' corrected age. No significant association was found for milk adiponectin concentrations. Conclusion: Milk IGF-1 and leptin concentrations in mothers of moderate-late preterm babies are associated with different growth and body composition through to 4 months' corrected age and these associations are often different in boys and girls. The sex-specific effects of nutrient and hormone exposure during early life in preterm infants warrants further investigation to optimize the nutritional care these infants receive, particularly in hospital, where the same nutrition is provided to boys and girls.
Publisher: Frontiers Media SA
Date: 02-06-2021
DOI: 10.3389/FENDO.2021.682726
Abstract: Obesity is a growing health problem worldwide. The renin-angiotensin system (RAS) is present in adipose tissue, and evidence suggests that it is involved in both diet-induced obesity and the inflammation associated with obesity. The present experiments determined the effect of (1) different angiotensin-converting enzyme (ACE) inhibitors (captopril, perindopril, enalapril) and angiotensin receptor blockers (ARBs: telmisartan, losartan) on adiposity of mice fed a high-fat diet for 28 days (2) acute treatment with the ACE-inhibitor captopril on gene expression of inflammatory markers in mice fed a high-fat diet (HFD) and (3) short-term (2 days) and chronic (28 days) treatment of ACE-inhibition on energy expenditure (EE) and energy balance in mice fed HFD ad libitum (AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group). Body weight, food intake, adiposity and plasma leptin were lower in ACE inhibitor or ARB-treated groups over 28 days compared with HFD untreated mice. Short-term treatment with captopril led to increased EE relative to the level in the PF group. After 28 days, EE was lower in both captopril-treated and PF mice compared with AL, but the effect was greater in the captopril-treated group. Adiponectin was elevated in captopril-treated mice, but not in PF mice, after both 2 and 28 days. Additionally, acute RAS blockade in HFD-fed mice reduced mRNA expression for MCP-1, IL-6, TLR4, and leptin in adipose tissue relative to values in untreated groups. These data demonstrate that ACE inhibition and angiotensin receptor blockade reduce food intake to produce weight loss and suggest that the anti-inflammatory effects of ACE inhibition may be independent of weight loss.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.METABOL.2005.02.012
Abstract: Dietary fatty acids regulate the abundance and activity of various proteins involved in the regulation of fat oxidation by functioning as regulators of gene transcription. To determine whether the transcription of key lipid metabolic proteins necessary for fat metabolism within human skeletal muscle are regulated by acute elevations in circulating free fatty acid (FFA) concentrations, 7 healthy men underwent 3 randomized resting infusions of Intralipid (20%) with heparin sodium, saline and heparin sodium, or saline only for 5 hours. These infusions significantly elevated plasma FFA concentrations by 15-fold (to 1.67 +/- 0.13 mmol/L) in the Intralipid infusion trial, with modest elevations observed in the saline and heparin sodium and saline alone infusion groups (0.67 +/- 0.09 and 0.49 +/- 0.087 mmol/L, P < .01 both vs Intralipid infusion). Analysis of messenger RNA (mRNA) concentration demonstrated that pyruvate dehydrogenase kinase isoform 4 (PDK4) mRNA, a key negative regulator of glucose oxidation, was increased in all trials with a 24-fold response after Intralipid infusion, 15-fold after saline and heparin infusion, and 9-fold after saline alone. The PDK4 increases were not significantly different between the 3 trials. The mRNA concentration of the major uncoupling protein within skeletal muscle, uncoupling protein 3, was not elevated in parallel to the increased plasma FFA as similar ( approximately 2-fold) increases were evident in all trials. Additional genes involved in lipid transport (fatty acid translocase/CD36), oxidation (carnitine palmitoyltransferase I), and metabolism (1-acylglycerol-3-phosphate O -acyltransferase 1, hormone-sensitive lipase, and peroxisomal proliferator-activated receptor-gamma coactivator-1alpha) were not altered by increased circulating FFA concentrations. The present data demonstrate that of the genes analyzed that encode proteins that are key regulators of lipid homeostasis within skeletal muscle, only the PDK4 gene is uniquely sensitive to increasing FFA concentrations after increased plasma FFA achieved by intravenous lipid infusion.
Publisher: Elsevier BV
Date: 06-2018
Publisher: Springer Science and Business Media LLC
Date: 04-06-2010
Abstract: Lipid droplet (LD) formation and size regulation reflects both lipid influx and efflux, and is central in the regulation of adipocyte metabolism, including adipokine secretion. The length and degree of dietary fatty acid (FA) unsaturation is implicated in LD formation and regulation in adipocytes. The aims of this study were to establish the impact of eicosapentaenoic acid (EPA C20:5n-3) in comparison to SFA (STA stearic acid, C18:0) and MUFA (OLA oleic acid, C18:1n-9) on 3T3-L1 adipocyte LD formation, regulation of genes central to LD function and adipokine responsiveness. Cells were supplemented with 100 μM FA during 7-day differentiation. EPA markedly reduced LD size and total lipid accumulation, suppressing PPARγ, Cidea and D9D/SCD1 genes, distinct from other treatments. These changes were independent of alterations of lipolytic genes, as both EPA and STA similarly elevated LPL and HSL gene expressions. In response to acute lipopolysaccharide exposure, EPA-differentiated adipocytes had distinct improvement in inflammatory response shown by reduction in monocyte chemoattractant protein-1 and interleukin-6 and elevation in adiponectin and leptin gene expressions. This study demonstrates that EPA differentially modulates adipogenesis and lipid accumulation to suppress LD formation and size. This may be due to suppressed gene expression of key proteins closely associated with LD function. Further analysis is required to determine if EPA exerts a similar influence on LD formation and regulation in-vivo .
Publisher: S. Karger AG
Date: 2006
DOI: 10.1159/000095354
Abstract: i Background: /i Skeletal muscle mass is governed by multiple IGF-1-sensitive positive regulators of muscle-specific protein synthesis (myogenic regulatory factors which includes myoD, myogenin and Myf5) and negative regulators, including the atrogenic proteins myostatin, atrogin-1 and muscle ring finger 1 (MuRF-1). The coordinated control of these myogenic and atrogenic factors in human skeletal muscle following short-term fasting is currently unknown. i Method: /i Healthy adults (n = 6, age 27.6 years) undertook a 40-hour fast. Skeletal muscle biopsy (vastus lateralis) and venous blood s les were taken 3, 15 and 40 h into the fast after an initial standard high-carbohydrate meal. Gene expression of the myogenic regulator factors (myoD, myogenin and Myf5) and the atrogenic factors (myostatin, atrogin-1 and MuRF-1) were determined by real-time PCR analysis. Plasma myostatin and IGF-1 were determined by ELISA. i Results: /i There were no significant alterations in either the positive or negative regulators of muscle mass at either 15 or 40 h, when compared to gene expression measured 3 h after a meal. Similarly, plasma myostatin and IGF-1 were also unaltered at these times. i Conclusions: /i Unlike previous observations in catabolic and cachexic diseased states, short-term fasting (40 h) fails to elicit marked alteration of the genes regulating both muscle-specific protein synthesis or atrophy. Greater periods of fasting may be required to initiate coordinated inhibition of myogenic and atrogenic gene expression.
Publisher: Frontiers Media SA
Date: 07-06-2017
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: American Physiological Society
Date: 03-2018
DOI: 10.1152/JAPPLPHYSIOL.00803.2017
Abstract: Muscle disuse results in the loss of muscular strength and size, due to an imbalance between protein synthesis (MPS) and breakdown (MPB). Protein ingestion stimulates MPS, although it is not established if protein is able to attenuate muscle loss with immobilization (IM) or influence the recovery consisting of ambulatory movement followed by resistance training (RT). Thirty men (49.9 ± 0.6 yr) underwent 14 days of unilateral leg IM, 14 days of ambulatory recovery (AR), and a further six RT sessions over 14 days. Participants were randomized to consume an additional 20 g of dairy protein or placebo with a meal during the intervention. Isometric knee extension strength was reduced following IM (−24.7 ± 2.7%), partially recovered with AR (−8.6 ± 2.6%), and fully recovered after RT (−0.6 ± 3.4%), with no effect of supplementation. Thigh muscle cross-sectional area decreased with IM (−4.1 ± 0.5%), partially recovered with AR (−2.1 ± 0.5%), and increased above baseline with RT (+2.2 ± 0.5%), with no treatment effect. Myofibrillar MPS, measured using deuterated water, was unaltered by IM, with no effect of protein. During AR, MPS was increased only with protein supplementation. Protein supplementation did not attenuate the loss of muscle size and function with disuse or potentiate recovery but enhanced myofibrillar MPS during AR. NEW & NOTEWORTHY Twenty grams of daily protein supplementation does not attenuate the loss of muscle size and function induced by 2 wk of muscle disuse or potentiate recovery in middle-age men. Average mitochondrial but not myofibrillar muscle protein synthesis was attenuated during immobilization with no effect of supplementation. Protein supplementation increased myofibrillar protein synthesis during a 2-wk period of ambulatory recovery following disuse but without group differences in phenotype recovery.
Publisher: MDPI AG
Date: 14-12-2009
DOI: 10.3390/NU1020263
Publisher: MDPI AG
Date: 17-11-2020
DOI: 10.3390/NU12113529
Abstract: Multivitamin and mineral (MVM) supplements are frequently used amongst older populations to improve adequacy of micronutrients, including B-vitamins, but evidence for improved health outcomes are limited and deficiencies remain prevalent. Although this may indicate poor efficacy of supplements, this could also suggest the possibility for altered B-vitamin bioavailability and metabolism in older people. This open-label, single-arm acute parallel study, conducted at the Liggins Institute Clinical Research Unit in Auckland, compared circulatory and urinary B-vitamer responses to MVM supplementation in older (70.1 ± 2.7 y, n = 10 male, n = 10 female) compared to younger (24.2 ± 2.8 y, n = 10 male, n = 10 female) participants for 4 h after the ingestion of a single dose of a commercial MVM supplement and standardized breakfast. Older adults had a lower area under the curve (AUC) of postprandial plasma pyridoxine (p = 0.02) and pyridoxal-5′phosphate (p = 0.03) forms of vitamin B6 but greater 4-pyridoxic acid AUC (p = 0.009). Urinary pyridoxine and pyridoxal excretion were higher in younger females than in older females (time × age × sex interaction, p 0.05). Older adults had a greater AUC increase in plasma thiamine (p = 0.01), riboflavin (p = 0.009), and pantothenic acid (p = 0.027). In older adults, there was decreased plasma responsiveness of the ingested (pyridoxine) and active (pyridoxal-5′phosphate) forms of vitamin B6, which indicated a previously undescribed alteration in either absorption or subsequent metabolic interconversion. While these findings cannot determine whether acute B6 responsiveness is adequate, this difference may have potential implications for B6 function in older adults. Although this may imply higher B vitamin substrate requirements for older people, further work is required to understand the implications of postprandial differences in availability.
Publisher: Springer Science and Business Media LLC
Date: 2003
Publisher: Frontiers Media SA
Date: 24-04-2020
Publisher: Elsevier BV
Date: 09-2015
Abstract: Postprandial lipemia represents a risk factor for chronic diseases, including type 2 diabetes. Little is known about the effect of dietary fat on the plasma lipidome in the postprandial period. The objective of this study was to assess the effect of dairy fat and soy oil on circulating postprandial lipids in men. Men (40-60 y old, nonsmokers n = 16) were randomly assigned in a crossover design to consume 2 breakfast meals of dairy-based or soy oil-based foods. The changes in the plasma lipidome during the 4-h postprandial period were analyzed with electrospray ionization tandem mass spectrometry and included 316 lipid species in 23 classes and subclasses, representing sphingolipids, phospholipids, glycerolipids, and sterols. Nonparametric Friedman tests showed significant changes in multiple plasma lipid classes, subclasses, and species in the postprandial period after both dairy and soy meals. No difference was found in triglyceridemia after each meal. However, 6 endogenous lipid classes increased after dairy but decreased after soy (P < 0.05), including ether-linked phospholipids and plasmalogens and sphingomyelin (not present in soy), dihexosylceramide, and GM3 ganglioside. Phosphatidylcholine and phosphatidylinositol were not affected by the soy meal but were significantly elevated after the dairy meal (8.3% and 16%, respectively P < 0.05). The changes in postprandial plasma phospholipids in men relate to the diet composition and the relative size of the endogenous phospholipid pools. Despite similar lipemic responses as measured by changes in triglyceride concentrations, the differential responses to dairy and soy meals derived through lipidomic analysis of phospholipids suggest differences in the metabolism of soybean oil and dairy fat. The increased concentrations of plasmalogens, with potential antioxidant capacity, in the postprandial period after dairy but not soy meals may represent a further important difference in the response to these sources of fat. The trial was registered at www.anzctr.org.au as ACTRN12610000562077.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2023
DOI: 10.1007/S00421-022-05107-X
Abstract: Mitochondrial dynamics are regulated by the differing molecular pathways variously governing biogenesis, fission, fusion, and mitophagy. Adaptations in mitochondrial morphology are central in driving the improvements in mitochondrial bioenergetics following exercise training. However, there is a limited understanding of mitochondrial dynamics in response to inactivity. Skeletal muscle biopsies were obtained from middle-aged males (n = 24, 49.4 ± 3.2 years) who underwent sequential 14-day interventions of unilateral leg immobilisation, ambulatory recovery, and resistance training. We quantified vastus lateralis gene and protein expression of key proteins involved in mitochondrial biogenesis, fusion, fission, and turnover in at baseline and following each intervention. PGC1α mRNA decreased 40% following the immobilisation period, and was accompanied by a 56% reduction in MTFP1 mRNA, a factor involved in mitochondrial fission. Subtle mRNA decreases were also observed in TFAM (17%), DRP1 (15%), with contrasting increases in BNIP3L and PRKN following immobilisation. These changes in gene expression were not accompanied by changes in respective protein expression. Instead, we observed subtle decreases in NRF1 and MFN1 protein expression. Ambulatory recovery restored mRNA and protein expression to pre-intervention levels of all altered components, except for BNIP3L. Resistance training restored BNIP3L mRNA to pre-intervention levels, and further increased mRNA expression of OPA-1, MFN2, MTFP1, and PINK1 past baseline levels. In healthy middle-aged males, 2 weeks of immobilisation did not induce dramatic differences in markers of mitochondria fission and autophagy. Restoration of ambulatory physical activity following the immobilisation period restored altered gene expression patterns to pre-intervention levels, with little evidence of further adaptation to resistance exercise training.
Publisher: American Physiological Society
Date: 07-2014
DOI: 10.1152/JAPPLPHYSIOL.01299.2013
Abstract: Cyclooxygenase-1 and -2 pathway-derived prostaglandins (PGs) have been implicated in adaptive muscle responses to exercise, but the role of PGs in contraction-induced muscle signaling has not been determined. We investigated the effect of inhibition of cyclooxygenase-1 and -2 activities with the nonsteroidal anti-inflammatory drug ibuprofen on human muscle signaling responses to resistance exercise. Subjects orally ingested 1,200 mg ibuprofen (or placebo control) in three 400-mg doses administered ∼30 min before and ∼6 h and ∼12 h following a bout of unaccustomed resistance exercise (80% one repetition maximum). Muscle biopsies were obtained at rest (preexercise), immediately postexercise (0 h), 3 h postexercise, and at 24 h of recovery. In the placebo (PLA) group, phosphorylation of ERK1/2 (Thr202/Tyr204), ribosomal protein S6 kinase (RSK, Ser380), mitogen-activated kinase 1 (Mnk1, Thr197/202), and p70S6 kinase (p70S6K, Thr421/Ser424) increased at both 0 and 3 h postexercise, with delayed elevation of phospho (p)-p70S6K (Thr389) and p-rpS6 (Ser235/S36 and Ser240/244) at 3 h postexercise. Only p-ERK1/2 (Thr202/Tyr204) remained significantly elevated in the 24-h postexercise biopsy. Ibuprofen treatment prevented sustained elevation of MEK-ERK signaling at 3 h (p-ERK1/2, p-RSK, p-Mnk1, p-p70S6K Thr421/Ser424) and 24 h (p-ERK1/2) postexercise, and this was associated with suppressed phosphorylation of ribosomal protein S6 (Ser235/236 and Ser240/244). Early contraction-induced p-Akt (Ser473) and p-p70S6K (Thr389) were not influenced by ibuprofen, but p-p70S6K (Thr389) remained elevated 24 h postexercise only in those receiving ibuprofen treatment. Early muscle signaling responses to resistance exercise are, in part, ibuprofen sensitive, suggesting that PGs are important signaling molecules during early postexercise recovery.
Publisher: The Endocrine Society
Date: 09-2006
DOI: 10.1210/JC.2006-0638
Abstract: Context: Leptin is thought to regulate whole-body adiposity and insulin sensitivity, at least in part, by stimulating fatty acid metabolism via activation of AMP-kinase (AMPK) in skeletal muscle. Human obesity is associated with leptin resistance, and recent studies have demonstrated that hypothalamic expression of the suppressors of cytokine signaling 3 (SOCS3) regulates leptin sensitivity in rodents. Objective: The objective of the study was to investigate the effects of leptin on fatty acid oxidation and AMPK signaling in primary myotubes derived from lean and obese skeletal muscle and evaluate the contribution of SOCS3 to leptin resistance and AMPK signaling in obese humans. Results: We demonstrate that leptin stimulates AMPK activity and increases AMPK Thr172 and acetyl-CoA carboxylase-β Ser222 phosphorylation and fatty acid oxidation in lean myotubes but that in obese subjects leptin-dependent AMPK signaling and fatty acid oxidation are suppressed. Reduced activation of AMPK was associated with elevated expression of IL-6 (∼3.5-fold) and SOCS3 mRNA (∼2.5-fold) in myotubes of obese subjects. Overexpression of SOCS3 via adenovirus-mediated infection in lean myotubes to a similar degree as observed in obese myotubes prevented leptin but not AICAR (5-amino-imidazole-4-carboxamide-1-β-d-ribofuranoside) activation of AMPK signaling. Conclusions: These data demonstrate that SOCS3 inhibits leptin activation of AMPK. These data suggest that this impairment of leptin signaling in skeletal muscle may contribute to the aberrant regulation of fatty acid metabolism observed in obesity and that pharmacological activation of AMPK may be an effective therapy to bypass SOCS3-mediated skeletal muscle leptin resistance for the treatment of obesity-related disorders.
Publisher: MDPI AG
Date: 17-07-2019
DOI: 10.3390/NU11071636
Abstract: Hydrogen (H2) measurement in exhaled breath is a reliable and non-invasive method to diagnose carbohydrate malabsorption. Currently, breath H2 measurement is typically limited to clinic-based equipment. A portable breath analyser (AIRE, FoodMarble Digestive Health Limited, Dublin, Ireland) is a personalised device marketed for the detection and self-management of food intolerances, including lactose malabsorption (LM). Currently, the validity of this device for breath H2 analysis is unknown. In iduals self-reporting dairy intolerance (six males and six females) undertook a lactose challenge and a further seven in iduals (all females) underwent a milk challenge. Breath s les were collected prior to and at frequent intervals post-challenge for up to 5 h with analysis using both the AIRE and a calibrated breath hydrogen analyser (BreathTracker, QuinTron Instrument Company Inc., Milwaukee, WI, USA). A significant positive correlation (p 0.001, r 0.8) was demonstrated between AIRE and BreathTracker H2 values, after both lactose and milk challenges, although 26% of the AIRE readings demonstrated the maximum score of 10.0 AU. Based on our data, the cut-off value for LM diagnosis (25 ppm H2) using AIRE is 3.0 AU and it is effective for the identification of a response to lactose-containing foods in in iduals experiencing LM, although its upper limit is only 81 ppm.
Publisher: Wiley
Date: 19-08-2004
Publisher: Springer Science and Business Media LLC
Date: 04-09-2008
Abstract: Palatable food disrupts normal appetite regulation, which may contribute to the etiology of obesity. Neuropeptide Y (NPY) and cholecystokinin play critical roles in the regulation of food intake and energy homeostasis, while adiponectin and carnitine palmitoyltransferase (CPT) are important for insulin sensitivity and fatty acid oxidation. This study examined the impact of short- and long-term consumption of palatable high-fat diet (HFD) on these critical metabolic regulators. Male C57BL/6 mice were exposed to laboratory chow (12% fat), or cafeteria-style palatable HFD (32% fat) for 2 or 10 weeks. Body weight and food intake were monitored throughout. Plasma leptin, hypothalamic NPY and cholecystokinin, and mRNA expression of leptin, adiponectin, their receptors and CPT-1, in fat and muscles were measured. Caloric intake of the palatable HFD group was 2-3 times greater than control, resulting in a 37% higher body weight. Fat mass was already increased at 2 weeks plasma leptin concentrations were 2.4 and 9 times higher than control at 2 and 10 weeks, respectively. Plasma adiponectin was increased at 10 weeks. Muscle adiponectin receptor 1 was increased at 2 weeks, while CPT-1 mRNA was markedly upregulated by HFD at both time points. Hypothalamic NPY and cholecystokinin content were significantly decreased at 10 weeks. Palatable HFD induced hyperphagia, fat accumulation, increased adiponectin, leptin and muscle fatty acid oxidation, and reduced hypothalamic NPY and cholecystokinin. Our data suggest that the adaptive changes in hypothalamic NPY and muscle fatty acid oxidation are insufficient to reverse the progress of obesity and metabolic consequences induced by a palatable HFD.
Publisher: Wiley
Date: 30-06-2019
DOI: 10.14814/PHY2.14108
Publisher: Springer Science and Business Media LLC
Date: 13-01-2016
DOI: 10.1007/S00198-015-3473-7
Abstract: The molecular regulation of muscle function in knee osteoarthritis is unclear. Elevated muscle atrophy regulation marker expression was associated with reduced muscle strength in knee osteoarthritis. The level of protein expression appears to be different between muscle, knee joint and serum, suggesting that inflammation is regulated differently within these tissues. Impaired muscle function is common in knee osteoarthritis (OA). Numerous biochemical molecules have been implicated in the development of OA however, these have only been identified in the joint and serum. We compared the expression of interleukin-15 (IL-15) and Forkhead box protein-O1 (FoxO1) in muscle of patients with knee OA and asymptomatic in iduals and examined whether IL-15 was also present in the joint and serum. Muscle and blood s les were collected from 19 patients with knee OA and 10 age-matched asymptomatic in iduals. Synovial fluid and muscle biopsies were collected from the OA group during knee replacement surgery. IL-15 and FoxO1 were measured in the skeletal muscle. IL-15 abundance was also analysed in the serum of both groups and synovial fluid from the OA group. Knee extensor strength was measured and correlated with IL-15 and FoxO1 in the muscle. FoxO1 protein expression was higher (p = 0.04), whereas IL-15 expression was lower (p = 0.02) in the muscle of the OA group. Strength was also lower in the OA group and was inversely correlated with FoxO1 expression. No correlation was found between IL-15 in the joint, muscle or serum. Skeletal muscle, particularly the quadriceps, is affected in people with knee OA where elevated FoxO1 protein expression was associated with reduced muscle strength. While IL-15 protein expression in the muscle was lower in the knee OA group, no correlation was found between the expression of IL-15 protein in the muscle, joint and serum, which suggests that inflammation is regulated differently within these tissues. Australian Clinical Trials Registry (ACTR) number: ACTRN12613000467730 ( www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000467730&isBasic=True ).
Publisher: American Physiological Society
Date: 15-03-2012
DOI: 10.1152/AJPREGU.00336.2011
Abstract: Intense resistance exercise causes a significant inflammatory response. NF-κB has been identified as a prospective key transcription factor mediating the postexercise inflammatory response. The purpose of this study was to determine whether a single bout of intense resistance exercise regulates NF-κB signaling in human skeletal muscle. Muscle biopsy s les were obtained from the vastus lateralis of five recreationally active, but not strength-trained, males (21.9 ± 1.3 yr) prior to, and at 2 and 4 h following, a single bout of intense resistance exercise. A further five subjects (4 males, 1 female) (23 ± 0.89 yr) were recruited as a nonexercise control group to examine the effect of the muscle biopsy protocol on key markers of skeletal muscle inflammation. Protein levels of IκBα and phosphorylated NF-κB (p65), as well as the mRNA expression of inflammatory myokines monocyte chemoattractant protein 1 (MCP-1), IL-6, and IL-8 were measured. Additionally, NF-κB (p65) DNA binding to the promoter regions of MCP-1, IL-6, and IL-8 was investigated. IκBα protein levels decreased, while p-NF-κB (p65) protein levels increased 2 h postexercise and returned to near-baseline levels by 4-h postexercise. Immunohistochemical data verified these findings, illustrating an increase in p-NF-κB (p65) protein levels, and nuclear localization at 2 h postexercise. Furthermore, NF-κB DNA binding to MCP-1, IL-6, and IL-8 promoter regions increased significantly 2 h postexercise as did mRNA levels of these myokines. No significant change was observed in the nonexercise control group. These novel data provide evidence that intense resistance exercise transiently activates NF-κB signaling in human skeletal muscle during the first few hours postexercise. These findings implicate NF-κB in the transcriptional control of myokines known to be central to the postexercise inflammatory response.
Publisher: Elsevier BV
Date: 04-2021
DOI: 10.1093/JN/NXAA417
Publisher: Wiley
Date: 24-11-2020
DOI: 10.1002/JCSM.12636
Publisher: MDPI AG
Date: 06-01-2020
DOI: 10.3390/NU12010152
Abstract: While human milk composition is characterised by marked dynamicity, we are far from having a clear picture of what factors drive this variation. Hormones in human milk are known to vary according to specific maternal phenotypes, but limited evidence shows the infant also has a role in determining milk composition. The present study aimed to investigate the interplay between maternal and infant characteristics in relation to human milk hormonal profile. In total, 501 human milk s les from mothers recruited in the Finnish STEPS cohort study (Steps to the healthy development) were analysed. Pre-pregnancy and pregnancy maternal data, socioeconomic status and infant characteristics at birth were collated. Leptin, adiponectin, insulin-like growth factor-1 and cyclic Glycine-Proline in milk were measured. Multivariate analysis of variance (MANOVA) and linear regression were utilised for statistical analysis. Sex-specific interactions with maternal factors were observed, as the infant sex mediated associations between gestational diabetes and milk adiponectin (p = 0.031), birth-mode and total protein (p = 0.003), maternal education and insulin-like growth factor-1: cyclic Glycine-Proline ratio (p = 0.035). Our results suggest that changes in human milk composition are associated with interactions between maternal and infant characteristics and pathophysiological factors. Future work should expand on these findings and further explore the link between hormonal profiles in human milk and infant outcomes.
Publisher: Public Library of Science (PLoS)
Date: 09-06-2014
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1093/JN/NXZ099
Publisher: Springer Science and Business Media LLC
Date: 21-11-2016
Publisher: American Physiological Society
Date: 06-2006
DOI: 10.1152/AJPENDO.00530.2005
Abstract: To investigate the in vivo effects of resistance exercise on translational control in human skeletal muscle, we determined the phosphorylation of AMP-activated kinase (AMPK), eukaryotic initiation factor 4E-binding protein (4E-BP1), p70 85-S6 protein kinase (S6K1), and ribosomal S6 protein (S6). Furthermore, we investigated whether changes in the phosphorylation of S6K1 are muscle fiber type specific. Eight male subjects performed a single high-intensity resistance exercise session. Muscle biopsies were collected before and immediately after exercise and after 30 and 120 min of postexercise recovery. The phosphorylation statuses of AMPK, 4E-BP1, S6K1, and S6 were determined by Western blotting with phospho-specific and pan antibodies. To determine fiber type-specific changes in the phosphorylation status of S6K1, immunofluorescence microscopy was applied. AMPK phosphorylation was increased approximately threefold immediately after resistance exercise, whereas 4E-BP1 phosphorylation was reduced to 27 ± 6% of preexercise values. Phosphorylation of S6K1 at Thr 421 /Ser 424 was increased 2- to 2.5-fold during recovery but did not induce a significant change in S6 phosphorylation. Phosphorylation of S6K1 was more pronounced in the type II vs. type I muscle fibers. Before exercise, phosphorylated S6K1 was predominantly located in the nuclei. After 2 h of postexercise recovery, phospho-S6K1 was primarily located in the cytosol of type II muscle fibers. We conclude that resistance exercise effectively increases the phosphorylation of S6K1 on Thr 421 /Ser 424 , which is not associated with a substantial increase in S6 phosphorylation in a fasted state.
Publisher: Wiley
Date: 28-05-2009
DOI: 10.1111/J.1463-1326.2009.01042.X
Abstract: To investigate the effects of globular adiponectin (gAd) on gene expression and whether these effects are mediated through 3',5'-cyclic monophosphate-activated protein kinase in skeletal muscle myotubes obtained from lean, obese and obese diabetic in iduals. Rectus abdominus muscle biopsies were obtained from surgical patients to establish primary skeletal muscle cell cultures. Three distinct primary cell culture groups were established (lean, obese and obese diabetic n = 7 in each group). Once differentiated, these cultures were then exposed to gAd or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) for 6 h. Stimulation with gAd decreased pyruvate dehydrogenase kinase 4 (PDK4) gene expression in the obese and diabetic s les (p < or = 0.05) and increased cytochrome c oxidase (COX) subunit 4 (COXIV) gene expression in the myotubes derived from lean in iduals only (p < 0.05). AICAR treatment also decreased PDK4 gene expression in the obese- and diabetic-derived myotubes (p < or = 0.05) and increased the gene expression of the mitochondrial gene, COXIII, in the lean-derived s les only (p < 0.05). This study demonstrated distinct disparity between myotubes derived from lean compared with obese and obese diabetic in iduals following gAd and AICAR treatment. Further understanding of the regulation of PDK4 in obese and diabetic skeletal muscle and its interaction with adiponectin signalling is required as this appears to be an important early molecular event in these disease states that may improve blood glucose control and metabolic flux.
Publisher: Wiley
Date: 09-12-2011
DOI: 10.1002/MUS.21875
Abstract: The JAK/STAT signaling pathway is essential for myogenic regeneration and is regulated by a erse range of ligands, including interleukin-6 (IL-6) and platelet-derived growth factor-BB (PDGF-BB). Our aim was to evaluate the responsiveness of IL-6 and PDGF-BB to intense exercise, along with STAT3 activation, before and after 12 weeks of resistance training. In young men, IL-6 and PDGF-BB protein concentrations were quantified in biopsied muscle and increased at 3 h post-exercise (17.5-fold and 3-fold, respectively). The response was unaltered by 12 weeks of training. Similarly, STAT3 phosphorylation was elevated post-exercise (12.5-fold), irrespective of training status, as was the expression of downstream targets c-MYC (8-fold), c-FOS (4.5-fold), and SOCS3 (2.3-fold). Thus, intense exercise transiently increases IL-6 and PDGF-BB proteins, and STAT3 phosphorylation is increased. These responses are preserved after intense exercise. This suggests they are not modified by training and may be an essential component of the adaptive responses to intense exercise.
Publisher: Wiley
Date: 24-05-2004
Publisher: Elsevier BV
Date: 06-2002
Publisher: MDPI AG
Date: 02-04-2017
DOI: 10.3390/NU9040354
Publisher: Springer Science and Business Media LLC
Date: 23-06-2013
DOI: 10.1007/S00394-012-0396-3
Abstract: Despite the detailed knowledge of the absorption and incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids and red blood cells (RBC) in humans, very little is known about docosapentaenoic acid (DPA, 22:5 n-3). The aim of this study was to investigate the uptake and incorporation of pure DPA and EPA into human plasma and RBC lipids. Ten female participants received 8 g of pure DPA or pure EPA in randomized crossover double-blinded manner over a 7-day period. The placebo treatment was olive oil. Blood s les were collected at days zero, four and seven, following which the plasma and RBC were separated and used for the analysis of fatty acids. Supplementation with DPA significantly increased the proportions of DPA in the plasma phospholipids (PL) (by twofold) and triacylglycerol (TAG) fractions (by 2.3-fold, day 4). DPA supplementation also significantly increased the proportions of EPA in TAG (by 3.1-fold, day 4) and cholesterol ester (CE) fractions (by 2.0-fold, day 7) and of DHA in TAG fraction (by 3.1-fold, day 4). DPA proportions in RBC PL did not change following supplementation. Supplementation with EPA significantly increased the proportion of EPA in the plasma CE and PL fractions, (both by 2.7-fold, day 4 and day 7) and in the RBC PL (by 1.9-fold, day 4 and day 7). EPA supplementation did not alter the proportions of DPA or DHA in any lipid fraction. These results showed that within day 4 of supplementation, DPA and EPA demonstrated different and specific incorporation patterns. The results of this short-term study suggest that DPA may act as a reservoir of the major long-chain n-3 fatty acids (LC n-3 PUFA) in humans.
Publisher: Wiley
Date: 31-03-2009
Publisher: Springer Science and Business Media LLC
Date: 16-02-2022
Publisher: Frontiers Media SA
Date: 30-06-2020
Publisher: Wiley
Date: 08-2023
DOI: 10.14814/PHY2.15784
Abstract: Cold water immersion (CWI) following intense exercise is a common athletic recovery practice. However, CWI impacts muscle adaptations to exercise training, with attenuated muscle hypertrophy and increased angiogenesis. Tissue temperature modulates the abundance of specific miRNA species and thus CWI may affect muscle adaptations via modulating miRNA expression following a bout of exercise. The current study focused on the regulatory mechanisms involved in cleavage and nuclear export of mature miRNA, including DROSHA , EXPORTIN‐5 , and DICER . Muscle biopsies were obtained from the vastus lateralis of young males ( n = 9) at rest and at 2, 4, and 48 h of recovery from an acute bout of resistance exercise, followed by either 10 min of active recovery (ACT) at ambient temperature or CWI at 10°C. The abundance of key miRNA species in the regulation of intracellular anabolic signaling (miR‐1 and miR‐133a) and angiogenesis (miR‐15a and miR‐126) were measured, along with several gene targets implicated in satellite cell dynamics (NCAM and PAX7) and angiogenesis (VEGF and SPRED‐1). When compared to ACT, CWI suppressed mRNA expression of DROSHA (24 h p = 0.025 and 48 h p = 0.017), EXPORTIN‐5 (24 h p = 0.008), and DICER (24 h p = 0.0034). Of the analyzed miRNA species, miR‐133a (24 h p 0.001 and 48 h p = 0.007) and miR‐126 (24 h p 0.001 and 48 h p 0.001) remained elevated at 24 h post‐exercise in the CWI trial only. Potential gene targets of these miRNA, however, did not differ between trials. CWI may therefore impact miRNA abundance in skeletal muscle, although the precise physiological relevance needs further investigation.
Publisher: American Physiological Society
Date: 02-2017
Publisher: Springer Science and Business Media LLC
Date: 07-07-2018
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.APPET.2021.105871
Abstract: This study aimed to identify biomarkers of appetite response, modelled using a dose-rising whey protein preload intervention. Female participants (n = 24) with body mass index (BMI) between 23 and 40 kg/m
Publisher: American Physiological Society
Date: 05-2020
DOI: 10.1152/JAPPLPHYSIOL.00032.2020
Abstract: Small regulatory peptides encoded within the mitochondrial genome (mitochondrial-derived peptides) have been shown to have cellular cyto- and metabolo-protective roles that parallel those of exercise. Here we provide evidence that humanin and SHLP6 are exercise-sensitive mitochondrial derived peptides. Studies to determine whether mitochondrial-derived peptides play a role in regulating exercise-induced adaptations are warranted.
Publisher: Wiley
Date: 30-04-2002
Publisher: Frontiers Media SA
Date: 18-11-2016
Publisher: American Physiological Society
Date: 02-2006
DOI: 10.1152/AJPREGU.00172.2005
Abstract: This study investigated effects of prolonged submaximal exercise on Na + -K + -ATPase mRNA and protein expression, maximal activity, and content in human skeletal muscle. We also investigated the effects on mRNA expression of the transcription initiator gene, RNA polymerase II (RNAP II), and key genes involved in protein translation, eukaryotic initiation factor-4E (eIF-4E) and 4E-binding protein 1 (4E-BP1). Eleven subjects (6 men, 5 women) cycled at 75.5% (SD 4.8%) peak O 2 uptake and continued until fatigue. A vastus lateralis muscle biopsy was taken at rest, fatigue, and 3 and 24 h postexercise. We analyzed muscle for Na + -K + -ATPase α 1 , α 2 , α 3 , β 1 , β 2 , and β 3 , as well for RNAP II, eIF-4E, and 4E-BP1 mRNA expression by real-time RT-PCR and Na + -K + -ATPase isoform protein abundance using immunoblotting. Muscle homogenate maximal Na + -K + -ATPase activity was determined by 3 -O-methylfluorescein phosphatase activity and Na + -K + -ATPase content by [ 3 H]ouabain binding. Cycling to fatigue [54.5 (SD 20.6) min] immediately increased α 3 ( P = 0.044) and β 2 mRNA ( P = 0.042) by 2.2- and 1.9-fold, respectively, whereas α 1 mRNA was elevated by 2.0-fold at 24 h postexercise ( P = 0.036). A significant time main effect was found for α 3 protein abundance ( P = 0.046). Exercise transiently depressed maximal Na + -K + -ATPase activity ( P = 0.004), but Na + -K + -ATPase content was unaltered throughout recovery. Exercise immediately increased RNAP II mRNA by 2.6-fold ( P = 0.011) but had no effect on eIF-4E and 4E-BP1 mRNA. Thus a single bout of prolonged submaximal exercise induced isoform-specific Na + -K + -ATPase responses, increasing α 1 , α 3 , and β 2 mRNA but only α 3 protein expression. Exercise also increased mRNA expression of RNAP II, a gene initiating transcription, but not of eIF-4E and 4E-BP1, key genes initiating protein translation.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.NIOX.2009.06.002
Abstract: Nitric oxide (NO) has been implicated as an important signaling molecule in the insulin-independent, contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control in patients with type 2 diabetes (T2DM). The current study sought to determine whether the NO donor, sodium nitroprusside (SNP) increases glucose uptake in primary human skeletal muscle cells (HSkMC) derived from both healthy in iduals and patients with T2DM. Vastus lateralis muscle cell cultures were derived from seven males with T2DM (aged 54 +/-2 years, BMI 31.7 +/-1.2 kg/m(2), fasting plasma glucose 9.52+/-0.80 mmol/L) and eight healthy in iduals (aged 46 +/-2 years, BMI 27.1 +/- 1.5 kg/m(2), fasting plasma glucose 4.69+/-0.12 mmol/L). Cultures were treated with both therapeutic (0.2 and 2 microM) and supratherapeutic (3, 10 and 30 mM) concentrations of SNP. An additional NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) was also examined at a concentration of 50 microM. Glucose uptake was significantly increased following both 30 and 60 min incubations with the supratherapeutic SNP treatments (P=0.03) but not the therapeutic SNP doses (P=0.60) or SNAP (P=0.54). There was no difference in the response between the healthy and T2DM cell lines with any treatment or dose. The current study demonstrates that glucose uptake is elevated by supratherapeutic, but not therapeutic doses of SNP in human primary skeletal muscle cells derived from both healthy volunteers and patients with T2D. These data confirm that nitric oxide donors have potential therapeutic utility to increase glucose uptake in humans, but that SNP only achieves this in supratherapeutic doses. Further study to delineate mechanisms and the therapeutic window is warranted.
Publisher: Cold Spring Harbor Laboratory
Date: 23-12-2019
DOI: 10.1101/2019.12.22.886432
Abstract: Healthy aging can be promoted by enhancing metabolic fitness and physical capacity ( 1, 2 ). Mitochondria are chief metabolic organelles with strong implications in aging ( 3–8 ). In addition to their prominent role in bioenergetics, mitochondria also coordinate broad physiological functions by communicating to other cellular compartments or distal cells using multiple factors ( 9, 10 ), including peptides that are encoded within their own independent genome ( 11, 12 ). However, it is unknown if aging is actively regulated by factors encoded in the mitochondrial genome. MOTS-c is a mitochondrial-encoded peptide that regulates metabolic homeostasis ( 13, 14 ), in part, by translocating to the nucleus to regulate adaptive nuclear gene expression in response to cellular stress ( 15–17 ). Here, we report that MOTS-c is an exercise-induced mitochondrial-encoded peptide that significantly enhanced physical performance when administered to young (2 mo.), middle-aged (12 mo.), and old (22 mo.) mice. In humans, we found that endogenous MOTS-c levels significantly increased in response to exercise in skeletal muscle (11.9-fold) and in circulation (1.5-fold). Systemic MOTS-c treatment in mice significantly enhanced the performance on a treadmill of all age groups (~2-fold). MOTS-c regulated (i) nuclear genes, including those related to metabolism and protein homeostasis, (ii) glucose and amino acid metabolism in skeletal muscle, and (iii) myoblast adaptation to metabolic stress. Late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) improved physical capacity and trended towards increasing lifespan. Our data indicate that aging is regulated by genes that are encoded not only in the nuclear genome ( 18, 19 ), but also in the mitochondrial genome. Considering that aging is the major risk factor for multiple chronic diseases ( 20, 21 ), our study provides new grounds for further investigation into mitochondrial-encoded regulators of healthy lifespan.
Publisher: Frontiers Media SA
Date: 12-06-2019
Publisher: MDPI AG
Date: 30-09-2021
DOI: 10.3390/NU13103479
Abstract: A high protein intake at old age is important for muscle protein synthesis, however, this could also trigger protein oxidation with the potential risk for DNA damage. The aim of this study was to investigate whether an increased protein intake at recommended level or well above would affect DNA damage or change levels of reduced (GSH) and oxidised glutathione (GSSG) in community-dwelling elderly subjects. These analyses were performed in two randomized intervention studies, in Austria and in New Zealand. In both randomized control trials, the mean protein intake was increased with whole foods, in the New Zealand study (n = 29 males, 74.2 ± 3.6 years) to 1.7 g/kg body weight/d (10 weeks intervention p 0.001)) in the Austrian study (n = 119 males and females, 72.9 ± 4.8 years) to 1.54 g/kg body weight/d (6 weeks intervention p 0.001)). In both studies, single and double strand breaks and as formamidopyrimidine—DNA glycosylase-sensitive sites were investigated in peripheral blood mononuclear cells or whole blood. Further, resistance to H2O2 induced DNA damage, GSH, GSSG and CRP were measured. Increased dietary protein intake did not impact on DNA damage markers and GSH/GSSG levels. A seasonal-based time effect (p 0.05), which led to a decrease in DNA damage and GSH was observed in the Austrian study. Therefore, increasing the protein intake to more than 20% of the total energy intake in community-dwelling seniors in Austria and New Zealand did not increase measures of DNA damage, change glutathione status or elevate plasma CRP.
Publisher: BMJ
Date: 12-2020
DOI: 10.1136/BMJOPEN-2020-041015
Abstract: Maternal obesity during pregnancy is associated with adverse changes in body composition and metabolism in the offspring. We hypothesise that supplementation during pregnancy of overweight and obese women may help prevent the development of greater adiposity and metabolic dysfunction in children. Previous clinical trials investigating fish oil supplementation in pregnancy on metabolic outcomes and body composition of the children have not focused on the pregnancies of overweight or obese women. A double-blind randomised controlled trial of fish oil (providing 3 g/day of n-3 polyunsaturated fatty acids) versus an equal volume of olive oil (control) taken daily from recruitment until birth, and in breastfeeding mothers, further continued for 3 months post partum. Eligible women will have a singleton pregnancy at 12–20 weeks’ gestation and be aged 18–40 years with body mass index ≥25 kg/m 2 at baseline. We aim to recruit a minimum of 128 participants to be randomised 1:1. Clinical assessments will be performed at baseline and 30 weeks of pregnancy, including anthropometric measurements, fasting metabolic markers, measures of anxiety, physical activity, quality of life and dietary intake. Subsequent assessments will be performed when the infant is 2 weeks, 3 months and 12 months of age for anthropometry, body composition (dual-energy X-ray absorptiometry (DXA)) and blood s ling. The primary outcome of the study is a between-group difference in infant percentage body fatness, assessed by DXA, at 2 weeks of age. Secondary outcomes will include differences in anthropometric measures at each time point, percentage body fat at 3 and 12 months and homeostatic model assessment of insulin resistance at 3 months. Statistical analysis will be carried out on the principle of intention to treat. This trial was approved by the Northern A Health and Disabilities Ethics Committee, New Zealand Ministry of Health (17/NTA/154). Results will be published in a peer-reviewed journal. ACTRN12617001078347p Pre-results.
Publisher: MDPI AG
Date: 16-05-2023
DOI: 10.3390/NU15102325
Abstract: Background: β-cryptoxanthin is a dietary carotenoid for which there have been few studies on the safety and pharmacokinetics following daily oral supplementation. Methods: 90 healthy Asian women between 21 and 35 years were randomized into three groups: 3 and 6 mg/day oral β-cryptoxanthin, and placebo. At 2, 4, and 8 weeks of supplementation, plasma carotenoid levels were measured. The effects of β-cryptoxanthin on blood retinoid-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition were investigated. Results: β-cryptoxanthin supplementation for 8 weeks (3 and 6 mg/day) was found to be safe and well tolerated. Plasma β-cryptoxanthin concentration was significantly higher in the 6 mg/day group (9.0 ± 4.1 µmol/L) compared to 3 mg/day group (6.0 ± 2.6 µmol/L) (p 0.03), and placebo (0.4 ± 0.1 µmol/L) (p 0.001) after 8 weeks. Plasma all-trans retinol, α-cryptoxanthin, α-carotene, β-carotene, lycopene, lutein, and zeaxanthin levels were not significantly changed. No effects were found on blood retinol-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition. Conclusions: Oral β-cryptoxanthin supplementation over 8 weeks lead to high plasma concentrations of β-cryptoxanthin, with no impact on other carotenoids, and was well tolerated in healthy women.
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.PLEFA.2011.06.002
Abstract: Previous studies have shown that Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) exhibit triacylglycerol (TAG) lowering effect in vitro and in vivo by down-regulating the Sterol Regulating Element Binding Protein (SREBP-1c) and reducing the expression levels of lipogenic genes. However, there is no evidence on the effect of Docosapentaenoic Acid (DPA) on SREBP-1c expression levels. DPA is a long chain n-3 fatty acid present in our diet through fish, red meat and milk of ruminant animals. Therefore, this study aimed to elucidate the effect of DPA on liver fatty acid synthesis in an in vitro model using rat liver cells. Our results suggested that DPA incubation (50μM) for 48h (like EPA and DHA) caused a significant decrease in the mRNA expression levels of SREBP-1c, 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A reductase (HMG-CoA reductase), Acetyl Coenzyme A Carboxylase (ACC-1) and Fatty Acid Synthase (FASn) compared with Oleic Acid (OA) and also a decrease in the protein levels of SREBP-1 and ACC-1. A time-course fatty acid analysis showed that DPA and EPA are interconvertable in the cells however, after 8h of incubation with DPA, the cell phospholipids contained mainly DPA. The gene expression profiling of the lipogenic genes repeated at 8h confirmed that the inhibitory effect of DPA on mRNA expression levels of the lipogenic genes was most likely due to DPA itself and not due to its conversion into EPA.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.ORCP.2006.10.003
Abstract: To investigate the effects of leptin on the mRNA abundance of key genes involved in fatty acid oxidation and mitochondrial biogenesis in cultured skeletal muscle myotubes derived from lean and obese in iduals. Rectus abdominus muscle biopsies were obtained from surgical patients to establish primary skeletal muscle cell cultures. Two distinct primary cell culture groups were established (Lean and Obese) n = 7 in each group. Differentiated cultures were then exposed to leptin (2.5 μg/ml) for 6 h. mRNA expression was subsequently measured by real-time PCR analysis. Basal mRNA expression of βHAD, COXIII, COXIV, PGC-1α and SOCS3 in the cultured human skeletal muscle myotubes were similar, however, PDK4 mRNA was elevated (P < 0.05) in the myotubes derived from obese in iduals. The addition of leptin resulted in a 2.5-fold increase in COXIV mRNA expression in the myotubes derived from Lean in iduals only (P < 0.05). There was also a tendency for leptin to increase COXIII, βHAD and PDK4 mRNA expression in this same group. Leptin had no impact on the gene expression of all measured transcripts in myotubes derived from obese in iduals. Short-term exposure of human skeletal muscle myotubes to leptin stimulated the expression of the mitochondrial enzyme COXIV in myotubes derived from lean in iduals, an effect that was abrogated in myotubes derived from obese in iduals. These data demonstrate a novel capacity for leptin to increase mitochondrial biogenesis and thus, a possible increased capacity for lipid oxidation and the persistence of a defect in leptin signalling in human myotubes cultured from obese in iduals.
Publisher: Springer Science and Business Media LLC
Date: 21-01-2015
DOI: 10.1038/SREP07928
Abstract: We evaluated the quality and content of fish oil supplements in New Zealand. All encapsulated fish oil supplements marketed in New Zealand were eligible for inclusion. Fatty acid content was measured by gas chromatography. Peroxide values (PV) and anisidine values (AV) were measured and total oxidation values (Totox) calculated. Only 3 of 32 fish oil supplements contained quantities of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that were equal or higher than labelled content, with most products tested (69%) containing %. The vast majority of supplements exceeded recommended levels of oxidation markers. 83% products exceeded the recommended PV levels, 25% exceeded AV thresholds and 50% exceeded recommended Totox levels. Only 8% met the international recommendations, not exceeding any of these indices. Almost all fish oil supplements available in the New Zealand market contain concentrations of EPA and DHA considerably lower than claimed by labels. Importantly, the majority of supplements tested exceeded the recommended indices of oxidative markers. Surprisingly, best-before date, cost, country of origin and exclusivity were all poor markers of supplement quality.
Publisher: MDPI AG
Date: 02-06-2016
DOI: 10.3390/NU8060338
Publisher: Wiley
Date: 11-2006
DOI: 10.1038/OBY.2006.221
Abstract: This study aimed to investigate the regulation of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) gene expression in primary skeletal muscle myotubes, derived from human donors, after exposure to globular adiponectin (gAd) and leptin. Four distinct primary cell culture groups were established [Lean, Obese, Diabetic, Weight Loss (Wt Loss) n = 7 in each] from rectus abdominus muscle biopsies obtained from surgical patients. Differentiated myotube cultures were exposed to gAd (0.1 microg/mL) or leptin (2.5 microg/mL) for 6 hours. AdipoR1 and AdipoR2 gene expression was measured by real-time polymerase chain reaction analysis. AdipoR1 mRNA expression in skeletal muscle myotubes derived from Lean subjects (p < 0.05) was stimulated 1.8-fold and 2.5-fold with gAd and leptin, respectively. No increase in AdipoR1 gene expression was measured in myotubes derived from Obese, Diabetic, or Wt Loss subjects. AdipoR2 mRNA expression was unaltered after gAd and leptin exposure in all myotube groups. Adiponectin and leptin are rapid and potent stimulators of AdipoR1 in myotubes derived from lean healthy in iduals. This effect was abolished in myotubes derived from obese, obese diabetic subjects, and obese-prone in iduals who had lost significant weight after bariatric surgery. The incapacity of skeletal muscle of obese and diabetic in iduals to respond to exogenous adiponectin and leptin may be further suppressed as a result of impaired regulation of the AdipoR1 gene.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.PLIPRES.2010.07.004
Abstract: This article summarizes the current knowledge available on metabolism and the biological effects of n-3 docosapentaenoic acid (DPA). n-3 DPA has not been extensively studied because of the limited availability of the pure compound. n-3 DPA is an elongated metabolite of EPA and is an intermediary product between EPA and DHA. The literature on n-3 DPA is limited, however the available data suggests it has beneficial health effects. In vitro n-3 DPA is retro-converted back to EPA, however it does not appear to be readily metabolised to DHA. In vivo studies have shown limited conversion of n-3 DPA to DHA, mainly in liver, but in addition retro-conversion to EPA is evident in a number of tissues. n-3 DPA can be metabolised by lipoxygenase, in platelets, to form ll-hydroxy-7,9,13,16,19- and 14-hydroxy-7,10,12,16,19-DPA. It has also been reported that n-3 DPA is effective (more so than EPA and DHA) in inhibition of aggregation in platelets obtained from rabbit blood. In addition, there is evidence that n-3 DPA possesses 10-fold greater endothelial cell migration ability than EPA, which is important in wound-healing processes. An in vivo study has reported that n-3 DPA reduces the fatty acid synthase and malic enzyme activity levels in n-3 DPA-supplemented mice and these effects were stronger than the EPA-supplemented mice. Another recent in vivo study has reported that n-3 DPA may have a role in attenuating age-related decrease in spatial learning and long-term potentiation. However, more research remains to be done to further investigate the biological effects of this n-3 VLCPUFA.
Publisher: American Physiological Society
Date: 02-2014
DOI: 10.1152/JAPPLPHYSIOL.00909.2013
Abstract: Reprogramming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. This study investigated the time course-dependent changes in the muscular transcriptome after an endurance exercise trial consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Skeletal muscle s les were taken at baseline, 3 h, 48 h, and 96 h postexercise from eight healthy, endurance-trained men. RNA was extracted from muscle. Differential gene expression was evaluated using Illumina microarrays and validated with qPCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Three hours postexercise, 102 gene sets were upregulated [family wise error rate (FWER), P 0.05], including groups of genes related with leukocyte migration, immune and chaperone activation, and cyclic AMP responsive element binding protein (CREB) 1 signaling. Forty-eight hours postexercise, among 19 enriched gene sets (FWER, P 0.05), two gene sets related to actin cytoskeleton remodeling were upregulated. Ninety-six hours postexercise, 83 gene sets were enriched (FWER, P 0.05), 80 of which were upregulated, including gene groups related to chemokine signaling, cell stress management, and extracellular matrix remodeling. These data provide comprehensive insights into the molecular pathways involved in acute stress, recovery, and adaptive muscular responses to endurance exercise. The novel 96 h postexercise transcriptome indicates substantial transcriptional activity potentially associated with the prolonged presence of leukocytes in the muscles. This suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 h after endurance exercise involving muscle damage.
Publisher: Oxford University Press (OUP)
Date: 02-2016
Publisher: Elsevier BV
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: JMIR Publications Inc.
Date: 03-06-2021
Abstract: he trend of flexitarian eating patterns is on the rise, with young adults among the biggest adopters claiming health and environmental reasons to reduce red meat intake. Nutrient-dense meat and animal products are often the lynchpin of these diets, even when consumed only occasionally and in moderate amounts. Red meat provides forms and concentrations of essential proteins, lipids, and micronutrients that are scarce in exclusively vegetarian regimens. he aim of this study is to consider the effects of moderate consumption of lean red meat as part of an otherwise vegetarian balanced diet and its impact on biomarkers of sustained health and well-being. cohort of healthy, young (20-34 years old, n=80) male and female participants will take part in a 2-arm, parallel randomized controlled trial (RCT) for a duration of 12 weeks, with a 3-month posttrial follow-up. The trial will commence with a 2-week assessment period followed by allocation to the intervention arms. The intervention will include the consumption of red meat or meat alternatives 3 times per week for 10 weeks. Blood s les of the participants will be collected to measure changes in erythrocyte fatty acid distribution, circulating amino acids, neurotransmitters, markers of mineral status, and inflammatory markers. Questionnaires to assess well-being and mental health will be undertaken every 2 weeks. Body composition, physical function, and blood parameters will be assessed at allocation (t sub /sub ), week 5 into the intervention (t sub /sub ), and post intervention (t sub /sub ). he protocol has been developed using the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) checklist and the outcomes will be reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines. The trial was approved by the New Zealand Ministry of Health’s Health and Disability Ethics Committees (protocol 20/STH/157). The results of this study will be communicated via publication. o our knowledge, this is the first RCT investigating the overarching health consequences of consuming pasture-fed red meat or no meat as part of a healthy diet. linicalTrials.gov NCT04869163 t2/show/NCT04869163 RR1-10.2196/30909
Publisher: MDPI AG
Date: 27-07-2010
DOI: 10.3390/NU2080781
Publisher: American Physiological Society
Date: 04-2007
DOI: 10.1152/JAPPLPHYSIOL.01260.2006
Abstract: To determine whether preexercise muscle glycogen content influences the transcription of several early-response genes involved in the regulation of muscle growth, seven male strength-trained subjects performed one-legged cycling exercise to exhaustion to lower muscle glycogen levels (Low) in one leg compared with the leg with normal muscle glycogen (Norm) and then the following day completed a unilateral bout of resistance training (RT). Muscle biopsies from both legs were taken at rest, immediately after RT, and after 3 h of recovery. Resting glycogen content was higher in the control leg (Norm leg) than in the Low leg (435 ± 87 vs. 193 ± 29 mmol/kg dry wt P 0.01). RT decreased glycogen content in both legs ( P 0.05), but postexercise values remained significantly higher in the Norm than the Low leg (312 ± 129 vs. 102 ± 34 mmol/kg dry wt P 0.01). GLUT4 (3-fold P 0.01) and glycogenin mRNA abundance (2.5-fold not significant) were elevated at rest in the Norm leg, but such differences were abolished after exercise. Preexercise mRNA abundance of atrogenes was also higher in the Norm compared with the Low leg [atrogin: ∼14-fold, P 0.01 RING (really interesting novel gene) finger: ∼3-fold, P 0.05] but decreased for atrogin in Norm following RT ( P 0.05). There were no differences in the mRNA abundance of myogenic regulatory factors and IGF-I in the Norm compared with the Low leg. Our results demonstrate that 1) low muscle glycogen content has variable effects on the basal transcription of select metabolic and myogenic genes at rest, and 2) any differences in basal transcription are completely abolished after a single bout of heavy resistance training. We conclude that commencing resistance exercise with low muscle glycogen does not enhance the activity of genes implicated in promoting hypertrophy.
Publisher: Cambridge University Press (CUP)
Date: 2015
DOI: 10.1017/JNS.2015.26
Publisher: CSIRO Publishing
Date: 2020
DOI: 10.1071/AN19427
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.BBI.2014.01.006
Abstract: Aging is associated with increased circulating pro-inflammatory and lower anti-inflammatory cytokines. Exercise training, in addition to improving muscle function, reduces these circulating pro-inflammatory cytokines. Yet, few studies have evaluated changes in the expression of cytokines within skeletal muscle after exercise training. The aim of the current study was to examine the expression of cytokines both at rest and following a bout of isokinetic exercise performed before and after 12weeks of resistance exercise training in young (n=8, 20.3±0.8yr) and elderly men (n=8, 66.9±1.6yr). Protein expression of various cytokines was determined in muscle homogenates. The expression of MCP-1, IL-8 and IL-6 (which are traditionally classified as 'pro-inflammatory') increased substantially after acute exercise. By contrast, the expression of the anti-inflammatory cytokines IL-4, IL-10 and IL-13 increased only slightly (or not at all) after acute exercise. These responses were not significantly different between young and elderly men, either before or after 12weeks of exercise training. However, compared with the young men, the expression of pro-inflammatory cytokines 2h post exercise tended to be greater in the elderly men prior to training. Training attenuated this difference. These data suggest that the inflammatory response to unaccustomed exercise increases with age. Furthermore, regular exercise training may help to normalize this inflammatory response, which could have important implications for muscle regeneration and adaptation in the elderly.
Publisher: Informa UK Limited
Date: 03-01-2017
Publisher: Springer Science and Business Media LLC
Date: 26-02-2019
DOI: 10.1038/S41598-019-39398-6
Abstract: An adequate supply of biotin is vital for the survival and pathogenesis of Staphylococcus aureus . The key protein responsible for maintaining biotin homeostasis in bacteria is the biotin retention protein A (BirA, also known as biotin protein ligase). BirA is a bi-functional protein that serves both as a ligase to catalyse the biotinylation of important metabolic enzymes, as well as a transcriptional repressor that regulates biotin biosynthesis, biotin transport and fatty acid elongation. The mechanism of BirA regulated transcription has been extensively characterized in Escherichia coli , but less so in other bacteria. Biotin-induced homodimerization of E. coli BirA ( Ec BirA) is a necessary prerequisite for stable DNA binding and transcriptional repression. Here, we employ a combination of native mass spectrometry, in vivo gene expression assays, site-directed mutagenesis and electrophoretic mobility shift assays to elucidate the DNA binding pathway for S. aureus BirA ( Sa BirA). We identify a mechanism that differs from that of Ec BirA, wherein Sa BirA is competent to bind DNA as a monomer both in the presence and absence of biotin and/or MgATP, allowing homodimerization on the DNA. Bioinformatic analysis demonstrated the Sa BirA sequence used here is highly conserved amongst other S. aureus strains, implying this DNA-binding mechanism is widely employed.
Publisher: Oxford University Press (OUP)
Date: 24-09-2021
Abstract: The prevalence of childhood obesity is increasing worldwide, and the children of women who are obese during pregnancy are at greatest risk. This risk may be mediated by exaggeration of the normal insulin resistance of pregnancy. Omega-3 (n-3) fats are insulin sensitizing. Supplementation during pregnancy may reduce metabolic risk and adiposity in the children. Though results from animal studies are encouraging, completed clinical trials have not demonstrated this benefit. However, to our knowledge, previous studies have not targeted women who are overweight or obese while pregnant—the group at greatest risk for insulin resistance and most likely to benefit from n-3. In this narrative review, the importance of performing clinical trials restricted to women who are overweight or obese is discussed, as is the potential importance of n-3 dose, oil source and quality, and the timing of the intervention.
Publisher: Wiley
Date: 29-11-2011
DOI: 10.1002/ACR.20625
Abstract: Patients with knee osteoarthritis (OA) are characterized by increased muscle inflammation and altered gait. We investigated the association between proinflammatory mediators in the vastus lateralis and physical function and gait in patients with knee OA. Nineteen patients with knee OA underwent gait analysis, assessment of self-reported pain and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), and a muscle biopsy that was taken during their knee replacement surgery. Muscle was analyzed for cellular protein inflammatory mediators, interleukin-6, monocyte chemotactic protein 1 (MCP-1), p65 NF-κB, signal transducer and activator of transcription 3 (STAT-3), and JNK-1. Sagittal plane knee function, including early stance knee range of motion (ROM) and knee sagittal plane impulse, was measured using a motion analysis system. Pearson's correlation was used to assess relationships between selected variables. Significant positive correlations were found between MCP-1 and self-perceived stiffness, physical function, and the total WOMAC score (P < 0.05). MCP-1 was also negatively correlated with early stance knee ROM (r = -0.52, P = 0.023). Reduced velocity was associated with elevated levels of p65 NF-κB and STAT-3 (P < 0.05). Knee sagittal plane impulse was negatively correlated with JNK-1 (P = 0.02), indicating reduction in knee impulse with an increased level of JNK-1. Increased levels of several proinflammatory mediators were correlated with altered knee function during walking as well as greater physical disability and slower gait velocity. Identification of the cellular and molecular mechanisms associated with muscle inflammation is important to better understand the underlying mechanism responsible for altered gait and function in patients with knee OA.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2017
DOI: 10.1007/S00421-017-3639-4
Abstract: The aim of the study was to determine whether higher fibrosis markers in skeletal muscle of older adults are accompanied by increased expression of components of the canonical TGF-β signal transduction pathway. Fourteen healthy young (21-35 years 9 males and 5 females) and seventeen older (55-75 years 9 males and 8 females) participants underwent vastus lateralis biopsies to determine intramuscular mRNA and protein expression of fibrogenic markers and TGF-β signaling molecules related to TGF-β1 and myostatin. Expression of mRNA encoding the pro-fibrotic factors axin 2, collagen III, β-catenin and fibronectin, were all significantly higher (all p < 0.05) in the older participants (350, 170, 298, and 641%, respectively). Furthermore, axin 2 and β-catenin mRNA were significantly higher in older females than older males (p < 0.05). Gene expression of ActRIIB, myostatin, and TGF-β1 were higher in older adults compared to younger adults (all p 0.05), whereas Smad3 protein phosphorylation was 48% lower (p < 0.05) in muscle from older adults. Increased abundance of mRNA of fibrotic markers was observed in muscle from older adults and was partly accompanied by altered abundance of pro-fibrotic ligands in a sex specific manner.
Publisher: American Physiological Society
Date: 15-06-2013
DOI: 10.1152/JAPPLPHYSIOL.00143.2013
Abstract: Neutrophils serve as an intriguing model for the study of innate immune cellular activity induced by physiological stress. We measured changes in the transcriptome of circulating neutrophils following an experimental exercise trial (EXTRI) consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Blood s les were taken at baseline, 3 h, 48 h, and 96 h post-EXTRI from eight healthy, endurance-trained, male subjects. RNA was extracted from isolated neutrophils. Differential gene expression was evaluated using Illumina microarrays and validated with quantitative PCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Blood concentrations of muscle damage indexes, neutrophils, interleukin (IL)-6 and IL-10 were increased ( P 0.05) 3 h post-EXTRI. Upregulated groups of functionally related genes 3 h post-EXTRI included gene sets associated with the recognition of tissue damage, the IL-1 receptor, and Toll-like receptor (TLR) pathways (familywise error rate, P value 0.05). The core enrichment for these pathways included TLRs, low-affinity immunoglobulin receptors, S100 calcium binding protein A12, and negative regulators of innate immunity, e.g., IL-1 receptor antagonist, and IL-1 receptor associated kinase-3. Plasma myoglobin changes correlated with neutrophil TLR4 gene expression ( r = 0.74 P 0.05). Neutrophils had returned to their nonactivated state 48 h post-EXTRI, indicating that their initial proinflammatory response was transient and rapidly counterregulated. This study provides novel insight into the signaling mechanisms underlying the neutrophil responses to endurance exercise, suggesting that their transcriptional activity was particularly induced by damage-associated molecule patterns, hypothetically originating from the leakage of muscle components into the circulation.
Publisher: Wiley
Date: 19-08-2002
DOI: 10.1046/J.1463-1326.2002.00216.X
Abstract: It has been reported previously that leptin may be involved in nicotine's ability to reduce body weight. Our aim was to investigate whether the anorexic action of nicotine is related to the actions of leptin by utilizing lean leptin-sensitive and obese leptin-resistant Psammomys obesus. Lean and obese P. obesus were assigned to receive nicotine sulphate at 6, 9 or 12 mg/day or saline (control) for 9 days (n = 6-10 in each group), administered using mini-osmotic pumps. Food intake, body weight, plasma leptin concentrations, plasma insulin and blood glucose were measured at baseline and throughout the study period. Nicotine treatment reduced food intake by up to 40% in lean and obese P. obesus. Plasma leptin levels fell significantly only in lean nicotine-treated animals, whereas no changes were observed in obese nicotine-treated animals. However, both lean and obese nicotine-treated animals had similar reductions in body weight. Our results show that nicotine has dramatic effects on food intake and body weight, however, these changes appear to be independent of the leptin signalling pathway.
Publisher: Springer Science and Business Media LLC
Date: 04-02-2020
DOI: 10.1186/S12263-020-0660-8
Abstract: Metabolic inflexibility is a characteristic of insulin resistance, limiting the ability to transiently regulate oxidative metabolism and gene expression in response to nutrient availability. Little is known of the flexibility of post-transcriptional regulation, including circulatory miRNAs (c-miRNAs). The abundances of targeted c-miRNAs, with reported functions in metabolic regulation, were analysed in response to a high-carbohydrate meal in healthy weight insulin-sensitive (IS) and overweight insulin-resistant (IR) women. Age-matched healthy weight IS ( n = 20, BMI = 24.3 ± 0.70) and overweight IR ( n = 20, BMI = 28.6 ± 0.67) women. An abundance of c-miRNAs was quantified prior to and following a high-carbohydrate breakfast meal (2500 kJ 50% carbohydrate, 20% fat and 27% protein). Target genes of the differentially regulated c-miRNA were measured in RNA extracted from circulatory peripheral blood mononuclear cells (PBMCs). In healthy weight IS women, both miR-15a-5p ( p = 0.03) and miR-17-5p ( p 0.01) levels were halved at 4 h post-meal. These miRNA remained unaltered following the same meal in the overweight IR women. Furthermore, amongst genes targeted by these miRNA, CPT1A ( p = 0.01) and IL8 ( p = 0.03) had also reduced expression 4 h post-meal only in the healthy weight IS women. The study findings provide preliminary evidence for a possible extension of metabolic inflexibility to include c-miRNAs. The clinical trial is registered with Australian New Zealand Clinical Trials Registry under Trial registration: ANZCTR: ACTRN12615001108505 . Registered on 21 October 2015.
Publisher: American Physiological Society
Date: 2013
DOI: 10.1152/AJPCELL.00038.2012
Abstract: Arachidonic acid (AA) is the metabolic precursor to a erse range of downstream bioactive lipid mediators. A positive or negative influence of in idual eicosanoid species [e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro . C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was lified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AA-stimulated growth was associated with markedly increased secretion of PGF 2α and PGE 2 however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway.
Publisher: Springer Science and Business Media LLC
Date: 22-04-2022
DOI: 10.1038/S41430-022-01119-0
Abstract: Self-reported digestive intolerance to dairy foods is common. As dairy can be an important source of dietary protein, this study aimed to identify whether milk protein digestion is compromised in in iduals with digestive intolerance. Adult women ( n = 40) were enroled in this double-blinded, randomised cross-over trial, with digestive symptoms characterised using a lactose challenge and self-reported digestive symptom questionnaire. Participants were classified as either lactose intolerant (LI, n = 10), non-lactose dairy intolerant (NLDI, n = 20) or dairy tolerant (DT, n = 10). In a randomised sequence, participants consumed three different kinds of milk (750 ml) conventional milk (CON), a2 Milk™ (A2M), and lactose-free conventional milk (LF-CON). Circulatory plasma amino acid (AA) concentrations were measured at baseline and every 30 min until 3 h post-ingestion. In all participants across all milk types, plasma AA concentrations (AUC 0-180 ) increased after milk ingestion with no significant differences in responses observed between milk types or participants ( P 0.05), with the exception of the suppressed lysine response in the DT group following A2M ingestion, relative to the other two groups and milk types ( P 0.05). Milk protein digestion, as determined by circulatory AAs, is largely unaffected by dairy- and lactose- intolerances.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.ARR.2014.05.001
Abstract: Progressive age-related changes in skeletal muscle mass and composition, underpin decreases in muscle function, which can inturn lead to impaired mobility and quality of life in older adults. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in skeletal muscle and are associated with aging. Accumulating evidence suggests that miRNAs play an important role in the age-related changes in skeletal muscle mass, composition and function. At the cellular level, miRNAs have been demonstrated to regulate muscle cell proliferation and differentiation. Furthermore, miRNAs are involved in the transitioning of muscle stem cells from a quiescent, to either an activated or senescence state. Evidence from animal and human studies has shown miRNAs are modulated in muscle atrophy and hypertrophy. In addition, miRNAs have been implicated in changes in muscle fiber composition, fat infiltration and insulin resistance. Both exercise and dietary interventions can combat age-related changes in muscle mass, composition and function, which may be mediated by miRNA modulation in skeletal muscle. Circulating miRNA species derived from myogenic cell populations represent potential biomarkers of aging muscle and the molecular responses to exercise or diet interventions, but larger validation studies are required. In future therapeutic approaches targeting miRNAs, either through exercise, diet or drugs may be able to slow down or prevent the age-related changes in skeletal muscle mass, composition, function, hence help maintain mobility and quality of life in old age.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.MCE.2006.12.038
Abstract: The endocannabinoids, a recently discovered endogenous, lipid derived, signaling system regulating energy metabolism, have effects on central and peripheral energy metabolism predominantly via the cannabinoid receptor type 1 (CB1). CB1 is expressed centrally in the hypothalamus and nucleus accumbens and peripherally in adipocytes and skeletal muscle. This study determined the effect of endocannabinoids on the expression of genes regulating energy metabolism in human skeletal muscle. Primary cultures of myotubes (lean and obese n=3/group) were treated with the cannabinoid receptor agonist, anandamide (AEA) (0.2 and 5microM) and the CB1 specific antagonist AM251 (0.2 and 5microM) separately and in combination for 24h. The expression of mRNA for AMP-activated protein kinase (AMPK) alpha 1 (alpha1) and alpha 2 (alpha2), pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha) were determined using 'Real Time' RT-PCR. AMPKalpha1 mRNA increased in lean and obese myotubes in response to AM251 (P<0.05). AEA inhibited the effect of AM251 on AMPKalpha1 mRNA levels in myotubes from lean and obese subjects (P<0.05) the dose-response curve was shifted to the left in the obese. In response to AM251, irrespective of the presence of AEA, PDK4 expression was decreased in lean and obese myotubes (P<0.05). Taken together these data suggest that endocannabinoids regulate pathways affecting skeletal muscle oxidation, effects particularly evident in myotubes from obese in iduals.
Publisher: Oxford University Press (OUP)
Date: 15-07-2022
Abstract: This manuscript is a response to concerns expressed in a letter by industry-based scientists Bannenberg and Rice in response to our recent narrative review. In the review, we largely discussed why supplementation with n-3 PUFA rich oils might have benefits to the body composition and metabolism of the offspring of overweight or obese pregnant women. Bannenberg and Rice raised concerns about a number of points that may be perceived as negative about the quality and functionality of commercial fish oils. We provide a refutation to their comments and a brief review of recent evidence regarding the n-3 PUFA content, and oxidative state of supplements available to consumers. From a clinical research perspective, there remains a need to exercise caution. An oil containing less n-3 PUFAs than expected may be ineffective, and lead to incorrect conclusions that n-3 PUFAs lack efficacy. Oxidized fish oil may be ineffective or even cause unwanted harm. Although we must not overinterpret limited evidence from animal models, we have a responsibility to minimize risk to study participants, especially those most vulnerable, such as pregnant women. Prior to selecting a fish oil to be used in a clinical trial, it is essential to independently verify the n-3 PUFA content of the oil, and that the oil is unoxidized.
Publisher: Oxford University Press (OUP)
Date: 03-2005
DOI: 10.1530/EJE.1.01872
Abstract: Objective : It has been suggested that adiponectin regulates plasma free fatty acid (FFA) clearance by stimulating FFA uptake and/or oxidation in muscle. We aimed to determine changes in plasma adiponectin concentration and adiponectin receptor 1 and 2 mRNA expression in skeletal muscle during and after prolonged exercise under normal, fasting conditions (high FFA trial HFA) and following pharmacological inhibition of adipose tissue lipolysis (low FFA trial LFA). Furthermore, we aimed to detect and locate adiponectin in skeletal muscle tissue. Methods : Ten subjects performed two exercise trials (120 min at 50% VO 2max ). Indirect calorimetry was used to determine total fat oxidation rate. Plasma s les were collected at rest, during exercise and during post-exercise recovery to determine adiponectin, FFA and glycerol concentrations. Muscle biopsies were taken to determine adiponectin protein and adiponectin receptor 1 and 2 mRNA expression and to localise intramyocellular adiponectin. Results : Basal plasma adiponectin concentrations averaged 6.57±0.7 and 6.63±0.8 mg/l in the HFA and LFA trials respectively, and did not change significantly during or after exercise. In the LFA trial, plasma FFA concentrations and total fat oxidation rates were substantially reduced. However, plasma adiponectin and muscle adiponectin receptor 1 and 2 mRNA expression did not differ between trials. Immunohistochemical staining of muscle cross-sections showed the presence of adiponectin in the sarcolemma of in idual muscle fibres and within the interfibrillar arterioles. Conclusion : Plasma adiponectin concentrations and adiponectin receptor 1 and 2 mRNA expression in muscle are not acutely regulated by changes in adipose tissue lipolysis and/or plasma FFA concentrations. Adiponectin is abundantly expressed in muscle, and, for the first time, it has been shown to be present in/on the sarcolemma of in idual muscle fibres.
Publisher: American Physiological Society
Date: 04-2021
DOI: 10.1152/AJPCELL.00284.2020
Abstract: Disuse-induced muscle atrophy is accompanied by a blunted postprandial response of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Conflicting observations exist as to whether postabsorptive mTORC1 pathway activation is also blunted by disuse and plays a role in atrophy. It is unknown whether changes in habitual protein intake alter mTORC1 regulatory proteins and how they may contribute to the development of anabolic resistance. The primary objective of this study was to characterize the downstream responsiveness of skeletal muscle mTORC1 activation and its upstream regulatory factors, following 14 days of lower limb disuse in middle-aged men (45–60 yr). The participants were further randomized to receive daily supplementation of 20 g/d of protein ( n = 12 milk protein concentrate) or isocaloric carbohydrate placebo ( n = 13). Immobilization reduced postabsorptive skeletal muscle phosphorylation of the mTORC1 downstream targets, 4E-BP1, P70S6K, and ribosomal protein S6 (RPS6), with phosphorylation of the latter two decreasing to a greater extent in the placebo, compared with the protein supplementation groups (37% ± 13% vs. 14% ± 11% and 38% ± 20% vs. 25% ± 8%, respectively). Sestrin2 protein was also downregulated following immobilization irrespective of supplement group, despite a corresponding increase in its mRNA content. This decrease in Sestrin2 protein was negatively correlated with the immobilization-induced change in the in silico-predicted regulator miR-23b-3p. No other measured upstream proteins were altered by immobilization or supplementation. Immobilization downregulated postabsorptive mTORC1 pathway activation, and 20 g/day of protein supplementation attenuated the decrease in phosphorylation of targets regulating muscle protein synthesis.
Publisher: Frontiers Media SA
Date: 06-12-2019
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.FREERADBIOMED.2018.06.012
Abstract: Extended periods of skeletal muscle disuse result in muscle atrophy. Following limb immobilization, increased mitochondrial reactive oxygen species (ROS) production may contribute to atrophy through increases in skeletal muscle protein degradation. However, the effect of skeletal muscle disuse on mitochondrial ROS production remains unclear. This study investigated the effect of immobilization, followed by two subsequent periods of restored physical activity, on mitochondrial H
Publisher: Elsevier
Date: 2015
DOI: 10.1016/BS.AFNR.2015.09.001
Abstract: The elderly are an increasing segment of the population. Despite the rapid gains in medical knowledge and treatments, older adults are more likely to experience chronic illnesses that decrease quality of life and accelerate mortality. Nutrition is a key modifiable lifestyle factor which greatly impacts chronic disease risk. Yet despite the importance of nutrition, relatively little is known of the impact of advancing age on the gastrointestinal function, the digestive responses, and the post-meal metabolic adaptations that occur in response to ingested food. Knowledge of the age-related differences in digestion and metabolism in the elderly is essential to the development of appropriate nutritional recommendations for the maintenance of optimal health and prevention of disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-12-2021
Publisher: Frontiers Media SA
Date: 29-03-2016
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C1FO10111K
Abstract: The aim of this study was to determine the effects of high-glucose, high-fructose and high-sucrose diets on weight gain, liver lipid metabolism and gene expression of proteins involved with hepatic fat metabolism. Rats were fed a diet containing either 60% glucose, 60% fructose, 60% sucrose, or a standard chow for 28 days. Results indicated that high-fructose and high-sucrose diets were associated with higher mRNA levels of gene transcripts involved with fat synthesis ACC, FAS and ChREBP, with no change in SREBP-1C mRNA. The protein level of ChREBP and SREBP1c was similar in liver homogenates from all groups, but were higher in nuclear fractions from the liver of high-fructose and high-sucrose fed rats. The mRNA level of gene transcripts involved with fat oxidation was the same in all three diets, whilst a high-fructose diet was associated with greater amount of mRNA of the fat transporter CD36. Despite the changes in mRNA of lipogenic proteins, the body weight of animals from each group was the same and the livers from rats fed high-fructose and high-sucrose diets did not contain more fat than control diet livers. In conclusion, changing the composition of the principal monosaccharide in the diet to a fructose containing sugar elicits changes in the level of hepatic mRNA of lipogenic and fat transport proteins and protein levels of their transcriptional regulators however this is not associated with any changes in body weight or liver fat content.
Publisher: Mary Ann Liebert Inc
Date: 08-2008
Abstract: Activation of the transcription factor signal transducers and activators of transcription (STAT) 3 is common to many inflammatory cytokines and growth factors, with recent evidence of involvement in skeletal muscle regeneration. The purpose of this study was to determine whether STAT3 signaling activation is regulated differentially, at rest and following intense resistance exercise, in aged human skeletal muscle. Skeletal muscle biopsies were harvested from healthy younger (n = 11, 20.4 +/- 0.8 years) and older men (n = 10, 67.4 +/- 1.3 years) under resting conditions and 2 h after the completion of resistance exercise. No differences were evident at rest, whereas the phosphorylation of STAT3 was significantly increased in old (23-fold) compared to young (5-fold) subjects after exercise. This correlated with significantly higher induction of the STAT3 target genes including interleukin-6 (IL-6), JUNB, c-MYC, and suppressor of cytokine signaling (SOCS) 3 mRNA in older subjects following exercise. Despite increased SOCS3 mRNA, cellular protein abundance was suppressed. SOCS3 protein is an important negative regulator of STAT3 activation and cytokine signaling. Thus, in aged human muscle, elevated responsiveness of the STAT3 signaling pathway and suppressed SOCS3 protein are evident following resistance exercise. These data suggest that enhanced STAT3 signaling responsiveness to proinflammatory factors may impact on mechanisms of muscle repair and regeneration.
Publisher: Springer Science and Business Media LLC
Date: 26-08-2008
DOI: 10.1038/IJO.2008.141
Abstract: Nutrition during critical periods in early life may increase the subsequent risk of obesity, hypertension and metabolic diseases in adulthood. Few studies have focused on the long-term consequences of poor nutrition during the suckling period on the susceptibility to developing obesity when exposed to a palatable cafeteria-style high-fat diet (CD) after weaning. This study examined the impact of early undernutrition, followed by CD exposure, on blood pressure, hormones and genes important for insulin sensitivity and metabolism and skeletal muscle mRNA expression of adiponectin receptor 1 (AdipoR1), carnitine palmitoyl-transferase I (CPT-1), cytochrome c oxidase 4 (COX4) and peroxisome proliferator-activated receptor alpha (PPARalpha). Following normal gestation, Sprague-Dawley rat litters were adjusted to 18 (undernourished) or 12 (control) pups. Rats were weaned (day 21) onto either palatable CD or standard chow. Early undernourished rats were significantly lighter than control by 17 days, persisting into adulthood only when animals were fed chow after weaning. Regardless of litter size, rats fed CD had doubled fat mass at 15 weeks of age, and significant elevations in plasma leptin, insulin and adiponectin. Importantly, undernutrition confined to the suckling period, elevated circulating adiponectin regardless of post-weaning diet. Blood pressure was reduced in early undernourished rats fed chow, and increased by CD. Early undernutrition was associated with long-term elevations in the expression of AdipoR1, CPT-1, COX4 and PPARalpha in skeletal muscle. This study demonstrates the important role of early nutrition on body weight and metabolism, suggesting early undernourishment enhances insulin sensitivity and fatty-acid oxidation. The long-term potential benefit of limiting nutrition in the early postnatal period warrants further investigation.
Publisher: Frontiers Media SA
Date: 16-06-2020
Publisher: Elsevier BV
Date: 09-2021
Publisher: Wiley
Date: 09-2015
DOI: 10.14814/PHY2.12511
Publisher: American Physiological Society
Date: 03-2011
DOI: 10.1152/AJPCELL.00549.2009
Abstract: Cyclooxygenase (COX) enzymes mediate the synthesis of proinflammatory prostaglandin (PG) species from cellular arachidonic acid. COX/PGs have been implicated in skeletal muscle growth/regeneration however, the mechanisms by which PGs influence skeletal muscle adaptation are poorly understood. The present study aimed to investigate PGF 2α signaling and its role in skeletal myotube hypertrophy. PGF 2α or the FP receptor agonist fluprostenol increased C2C12 myotube diameter. This effect was abolished by the FP receptor antagonist AL8810 and mammalian target of rapamycin (mTOR) inhibition. PGF 2α stimulated time- and dose-dependent increases in the phosphorylation of extracellular receptor kinase (ERK)1/2 (Thr202/Tyr204), p70S6 kinase (p70S6K) (Thr389 and Thr421/Ser424), and eukaryotic initiation factor 4G (eIF4G) (Ser1108) without influencing Akt (Ser473). Pretreatment with the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and the ERK inhibitor PD98059 blocked F prostanoid receptor signaling responses, whereas rapamycin blocked heightened p70S6K/eIF4G phosphorylation without influencing ERK1/2 phosphorylation. These data suggest that activation of the F prostanoid receptor is coupled to C2C12 myotube growth and intracellular signaling via a PI3K/ERK/mTOR-dependent pathway.
Publisher: American Dairy Science Association
Date: 06-2017
Abstract: Whey protein concentrate (WPC) is a high-quality dairy ingredient that is often included in formulated food products designed to stimulate muscle anabolism. Whey protein concentrate can be affected by UHT processing, and its sensory properties are not compatible with some formulated food products. Microparticulated WPC (mWPC) is a novel ingredient that is resistant to heat treatment and has enhanced sensory properties. When 16 healthy middle-aged men consumed 20 g of either WPC or mWPC, both proteins increased plasma essential AA and leucine concentrations with no detectable difference in curve kinetics. Myofibrillar protein synthesis was increased in both groups for 90 min after ingestion with no difference between groups. Ingestion of mWPC resulted in a muscle anabolic response that was equivalent to that of WPC over the full 210-min measurement period. Formulated products incorporating mWPC or standard WPC would provoke equivalent anabolic responses.
Publisher: Elsevier BV
Date: 07-2015
Abstract: Krill is an increasingly popular source of marine n-3 (ω-3) PUFA that is seen as a premium product. However, to our knowledge, the effect of krill-oil supplementation on insulin sensitivity in humans has not been reported. We assessed whether supplementation with a blend of krill and salmon (KS) oil [which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] affects insulin sensitivity in overweight men. The design was a randomized, double-blind, controlled crossover trial. A total of 47 men with a mean ± SD age of 46.5 ± 5.1 y, who were overweight [body mass index (in kg/m(2)) from 25 to 30] but otherwise healthy, received 5 1-g capsules of KS oil or a control (canola oil) for 8 wk and crossed over to another treatment after an 8-wk washout period. The primary outcome was insulin sensitivity assessed by using the Matsuda method from an oral-glucose-tolerance test. Secondary outcomes included lipid profiles, inflammatory markers, 24-h ambulatory blood pressure, and carotid artery intimamedia thickness. Unexpectedly, insulin sensitivity (per the Matsuda index) was 14% lower with the KS oil than with the control oil (P = 0.049). A mediation analysis showed that, after controlling for the likely positive effects of blood EPA and DHA (i.e., the omega-3 index), the reduction in insulin sensitivity after KS-oil supplementation was more marked [27% lower than with the control oil (P = 0.009)]. Supplementation with a blend of KS oil is associated with decreased insulin sensitivity. Thus, krill-oil supplementation in overweight adults could exacerbate risk of diabetes and cardiovascular disease. This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry as ACTRN12611000602921.
Publisher: American Physiological Society
Date: 07-2005
DOI: 10.1152/AJPREGU.00378.2004
Abstract: We investigated whether depressed muscle Na + -K + -ATPase activity with exercise reflected a loss of Na + -K + -ATPase units, the time course of its recovery postexercise, and whether this depressed activity was related to increased Na + -K + -ATPase isoform gene expression. Fifteen subjects performed fatiguing, knee extensor exercise at ∼40% maximal work output per contraction. A vastus lateralis muscle biopsy was taken at rest, fatigue, 3 h, and 24 h postexercise and analyzed for maximal Na + -K + -ATPase activity via 3- O-methylfluorescein phosphatase (3- O-MFPase) activity, Na + -K + -ATPase content via [ 3 H]ouabain binding sites, and Na + -K + -ATPase α 1 -, α 2 -, α 3 -, β 1 -, β 2 - and β 3 -isoform mRNA expression by real-time RT-PCR. Exercise [352 (SD 267) s] did not affect [ 3 H]ouabain binding sites but decreased 3- O-MFPase activity by 10.7 (SD 8)% ( P 0.05), which had recovered by 3 h postexercise, without further change at 24 h. Exercise elevated α 1 -isoform mRNA by 1.5-fold at fatigue ( P 0.05). This increase was inversely correlated with the percent change in 3- O-MFPase activity from rest to fatigue (%Δ3- O-MFPase rest-fatigue ) ( r = −0.60, P 0.05). The average postexercise (fatigue, 3 h, 24 h) α 1 -isoform mRNA was increased 1.4-fold ( P 0.05) and approached a significant inverse correlation with %Δ3- O-MFPase rest-fatigue ( r = −0.56, P = 0.08). Exercise elevated α 2 -isoform mRNA at fatigue 2.5-fold ( P 0.05), which was inversely correlated with %Δ3- O-MFPase rest-fatigue ( r = −0.60, P = 0.05). The average postexercise α 2 -isoform mRNA was increased 2.2-fold ( P 0.05) and was inversely correlated with the %Δ3- O-MFPase rest-fatigue ( r = −0.68, P 0.05). Nonsignificant correlations were found between %Δ3- O-MFPase rest-fatigue and other isoforms. Thus acute exercise transiently decreased Na + -K + -ATPase activity, which was correlated with increased Na + -K + -ATPase gene expression. This suggests a possible signal-transduction role for depressed muscle Na + -K + -ATPase activity with exercise.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.FOODCHEM.2015.03.059
Abstract: Oxidised lipid species, their bioavailability and impact on inflammatory responses from cooked beef steak are poorly characterised. Oxidised lipid species from pan-fried (PF) and sous-vide (SV) thermally processed beef were determined with UHPLC-ESI/MS. Twenty-three lipid oxidation products increased with thermal processing and differences between the PF and SV steaks were measured. Fifteen oxidised lipids were measured in post-meal plasma after a cross-over randomised clinical study. Postprandial plasma inflammatory markers tended to remain lower following the SV meal than the PF meal. High levels of conjugated dienes were measured in the HDL fraction, suggesting that the protective effect of HDL may extend to the reverse-transport of oxidised lipid species. Oxidised lipids in a single meal may influence postprandial oxidative stress and inflammation. Further studies are required to examine the lipid oxidative responses to increased dietary oxidative lipid load, including the reverse transport activity of HDL.
Publisher: Springer Science and Business Media LLC
Date: 1995
DOI: 10.1007/BF00838490
Abstract: CRBP-1, a cytosolic chaperone of vitamin A, is identified in a serious number of cancers however, its biological role in hepatocellular carcinoma (HCC) needs to be further explored. The aim of our present study is to explore the roles and mechanisms of CRBP-1 in regulating liver cancer by using in vitro and in vivo biology approaches. The expression level of CRBP-1 was detected using immunohistochemistry in HCC and matching adjacent non-tumorous liver tissues. Following established stable CRBP-1 overexpressed HCC cell lines, the cell growth and tumorigenicity were investigated both in vitro and in vivo. Intracellular retinoic acid was quantified by ELISA. The relationship between CRBP-1 and WIF1 was validated by using dual luciferase and ChIP analyses. The low expression of CRBP-1 was observed in HCC tissues compared to the normal liver tissues, while high CRBP-1 expression correlated with clinicopathological characteristics and increased overall survival in HCC patients. Overexpression of CRBP-1 significantly inhibited cell growth and tumorigenicity both in vitro and in vivo. Moreover, overexpression of CRBP-1 suppressed tumorsphere formation and cancer stemness related genes expression in HCC. Mechanically, CRBP-1 inhibited Wnt/β-catenin signaling pathway to suppress cancer cell stemness of HCC. Furthermore, our results revealed that CRBP-1 could increase the intracellular levels of retinoic acid, which induced the activation of RARs/RXRs leading to the transcriptional expression of WIF1, a secreted antagonist of the Wnt/β-catenin signaling pathway, by physically interacting with the region on WIF1 promoter. Our findings reveal that CRBP-1 is a crucial player in the initiation and progression of HCC, which provide a novel independent prognostic biomarker and therapeutic target for the diagnosis and treatment of HCC.
Publisher: Springer Science and Business Media LLC
Date: 20-01-2021
DOI: 10.1038/S41467-020-20790-0
Abstract: Healthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.
Publisher: Springer Science and Business Media LLC
Date: 23-01-2017
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.PLEFA.2013.07.006
Abstract: Storage of fat into lipid droplets (LDs) is the key step in adipogenesis. Previously the omega-3 polyunsaturated fatty acid (n-3PUFA) eicosapentaenoic acid (EPA C20:5n-3) has been shown to suppress LD formation, yet the actions of other n-3PUFA is unknown. Here, we examined the impact of the three major long chain n-3PUFA EPA, docosapentaenoic acid (DPA C22:5n-3) and docosahexaenoic acid (DHA C22:6n-3) on LD formation in 3T3-L1 adipocytes. Cells were supplemented with 100µM fatty acid during differentiation. All n-3PUFA significantly reduced LD formation and the metabolic disorder marker, SCD1, in comparison to stearic acid (STA C18:0). This action was more potent for DHA than either EPA or DPA. Furthermore, DHA significantly increased lipolysis and ATGL gene and protein expression but reduced the gene expression of three proteins related to LD formation (Perilipin A, Caveolin-1 and Cidea), compared with other n-3PUFA. Thus, DHA, above EPA and DPA, markedly suppressed fat storage in LDs in in-vitro adipocytes.
Publisher: American Physiological Society
Date: 02-2019
DOI: 10.1152/AJPCELL.00395.2018
Abstract: Loss of muscle size and strength with aging is a major cause of morbidity. Although muscle size and strength are measured by imaging or fiber cross-sectional staining and exercise testing, respectively, the development of circulatory biomarkers for these phenotypes would greatly simplify identification of muscle function deficits. MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene translation and, thereby, contribute to muscle phenotype. To assess circulatory miRNAs (c-miRNAs) applicability as potential biomarkers of muscular phenotypes, fasting plasma and muscle s les were obtained from 50 middle-aged healthy men [mean (SD) age: 48.8 yr (SD 4.5) BMI: 26.6 kg/m 2 (SD 3.3)]. RT-PCR of 38 miRNAs with known regulatory function within skeletal muscle identified four c-miRNAs (miR-221, miR-451a, miR-361, and miR-146a) related to either total body lean mass, leg lean mass, and 50% thigh cross-sectional area (CSA), but not strength. There was no relationship with the expression of these miRNAs in muscle. Six miRNAs within muscle were correlated with whole body lean mass, leg lean mass, and isometric knee extension torque (miR-133a and miR-146a), and 50% thigh CSA (miR-486, miR-208b, miR-133b, and miR-208a). Only miR-23b demonstrated a relationship between tissue and circulatory expression however, only 10% of the variance was explained. miR-146a in both plasma and muscle was related to phenotype however, no relationship between plasma and muscle expression was evident. A different subset of miRNAs correlated to muscle phenotype in muscle compared with plasma s les, suggesting that c-miRNA biomarkers of muscle phenotype are likely unrelated to muscle expression in healthy in iduals.
Publisher: American Physiological Society
Date: 03-2016
DOI: 10.1152/AJPREGU.00351.2015
Abstract: A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD 10% kcal fat), a CD supplemented with CLA (CLA 10% kcal fat, 1% total fat as CLA), a high-fat (HFD 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1β concentrations. Phosphorylation of NF-κBp65 (Ser 536 ) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development.
Publisher: American Physiological Society
Date: 09-2016
DOI: 10.1152/AJPREGU.00005.2016
Abstract: Fish oil is commonly taken by pregnant women, and supplements sold at retail are often oxidized. Using a rat model, we aimed to assess the effects of supplementation with oxidized fish oil during pregnancy in mothers and offspring, focusing on newborn viability and maternal insulin sensitivity. Female rats were allocated to a control or high-fat diet and then mated. These rats were subsequently randomized to receive a daily gavage treatment of 1 ml of unoxidized fish oil, a highly oxidized fish oil, or control (water) throughout pregnancy. At birth, the gavage treatment was stopped, but the same maternal diets were fed ad libitum throughout lactation. Supplementation with oxidized fish oil during pregnancy had a marked adverse effect on newborn survival at day 2, leading to much greater odds of mortality than in the control (odds ratio 8.26) and unoxidized fish oil (odds ratio 13.70) groups. In addition, maternal intake of oxidized fish oil during pregnancy led to increased insulin resistance at the time of weaning (3 wks after exposure) compared with control dams (HOMA-IR 2.64 vs. 1.42 P = 0.044). These data show that the consumption of oxidized fish oil is harmful in rat pregnancy, with deleterious effects in both mothers and offspring.
Publisher: American Physiological Society
Date: 07-2004
DOI: 10.1152/AJPENDO.00557.2003
Abstract: Changes in dietary macronutrient intake alter muscle and blood substrate availability and are important for regulating gene expression. However, few studies have examined the effects of diet manipulation on gene expression in human skeletal muscle. The aim of this study was to quantify the extent to which altering substrate availability impacts on subsequent mRNA abundance of a subset of carbohydrate (CHO)- and fat-related genes. Seven subjects consumed either a low- (LOW 0.7 g/kg body mass CHO) or high- (HIGH 10 g/kg body mass CHO) CHO diet for 48 h after performing an exhaustive exercise bout to deplete muscle glycogen stores. After intervention, resting muscle and blood s les were taken. Muscle was analyzed for the gene abundances of GLUT4, glycogenin, pyruvate dehydrogenase kinase-4 (PDK-4), fatty acid translocase (FAT/CD36), carnitine palmitoyltransferase I (CPT I), hormone-sensitive lipase (HSL), β-hydroxyacyl-CoA dehydrogenase (β-HAD), and uncoupling binding protein-3 (UCP3), and blood s les for glucose, insulin, and free fatty acid (FFA) concentrations. Glycogen-depleting exercise and HIGH-CHO resulted in a 300% increase in muscle glycogen content ( P 0.001) relative to the LOW-CHO condition. FFA concentrations were twofold higher after LOW- vs. HIGH-CHO ( P 0.05). The exercise-diet manipulation exerted a significant effect on transcription of all carbohydrate-related genes, with an increase in GLUT4 and glycogenin mRNA abundance and a reduction in PDK-4 transcription after HIGH-CHO (all P 0.05). FAT/CD36 ( P 0.05) and UCP3 ( P 0.01) gene transcriptions were increased following LOW-CHO. We conclude that 1) there was a rapid capacity for a short-term exercise and diet intervention to exert coordinated changes in the mRNA transcription of metabolic related genes, and 2) genes involved in glucose regulation are increased following a high-carbohydrate diet.
Publisher: Informa UK Limited
Date: 20-10-2015
Publisher: Springer Science and Business Media LLC
Date: 02-06-2004
Publisher: Bioscientifica
Date: 08-2003
Abstract: This study examined the actions of 17beta-estradiol (E(2)) and progesterone on the regulation of the peroxisome proliferator-activated receptors (PPARalpha and PPARgamma) family of nuclear transcription factors and the mRNA abundance of key enzymes involved in fat oxidation, in skeletal muscle. Specifically, carnitine palmitoyltransferase I (CPT I), beta-3-hydroxyacyl CoA dehydrogenase (beta-HAD), and pyruvate dehydrogenase kinase 4 (PDK4) were examined. Sprague-Dawley rats were ovariectomized and treated with placebo (Ovx), E(2), progesterone, or both hormones in combination (E+P). Additionally, sham-operated rats were treated with placebo (Sham) to serve as controls. Hormone (or vehicle only) delivery was via time release pellets inserted at the time of surgery, 15 days prior to analysis. E(2) treatment increased PPARalpha mRNA expression and protein content (P .05), compared with Ovx treatment. E(2) also resulted in upregulated mRNA of CPT I and PDK4 (P .05). PPARgamma mRNA expression was also increased (P .05) by E(2) treatment, although protein content remained unaltered. These data demonstrate the novel regulation of E(2) on PPARalpha and genes encoding key proteins that are pivotal in regulating skeletal muscle lipid oxidative flux.
Publisher: Wiley
Date: 13-11-2017
DOI: 10.1113/JP272881
Publisher: Bioscientifica
Date: 07-1998
Abstract: Insulin-like growth factor-binding protein-1 (IGFBP-1) production is increased by somatostatin and its analogues. In order to determine the time course and identify possible mechanisms of this increase in vivo we administered octreotide to rats and determined IGFBP-1 concentrations by RIA. After 60 min of anaesthesia, the mean baseline IGFBP-1 concentrations were 166 (95% confidence interval 123 to 225) ng/ml and increased in saline-infused animals to 729 (488 to 1086) ng/ml after 180 min. IGFBP-1 was stimulated transiently in response to octreotide, with circulating IGFBP-1 concentrations peaking at 1605 (1220 to 2111) ng/ml at 105 min during a continuous infusion of octreotide (100 micrograms/kg per h). In conscious chronically cannulated rats, baseline IGFBP-1 concentrations were 22 (18 to 28) ng/ml, 8-fold less than in the anaesthetised state, and were stimulated in the short term after administration of an octreotide bolus (100 micrograms/kg s.c.) to reach 88 (62 to 126) ng/ml at 60 min. A similar response was seen after i.v. administration to conscious rats. Intravenous bolus of octreotide (100 micrograms/kg) in rats anaesthetised for 3 h resulted in an increase in IGFBP-1 to peak at 1556 (1268 to 1910) ng/ml at 60 min. The IGFBP-1 response to octreotide was diminished in high-fat fed hyperinsulinaemic rats. The pattern of disappearance of iodinated IGFBP-1 from the circulation was not influenced by octreotide. The changes in GH, insulin and glucose concentrations alone did not sufficiently account for the patterns of response observed. We conclude that, in rats, octreotide stimulates IGFBP-1 acutely and this response is potentiated by factors related to anaesthesia.
Publisher: MDPI AG
Date: 12-10-2018
DOI: 10.3390/NU10101492
Abstract: Fortified milk drinks are predominantly manufactured from bovine (cow) sources. Alternative formulations include those prepared with hydrolysed bovine milk proteins or from alternate bovidae species, such as caprine (goat) milk. Currently, there is little data on protein digestive and metabolic responses following ingestion of fortified milk drinks. To examine the digestive and metabolic responses to commercially-available fortified milks, young adults (n = 15 males: 15 females), in a randomised sequence, ingested isonitrogenous quantities of whole cow-protein (WC), whole goat-protein (WG), or partially-hydrolysed whey cow-protein (HC), commercial fortified milks. Plasma amino acid (AA) and hormonal responses were measured at baseline and again at 5 h after ingestion. Paracetamol recovery, breath hydrogen, and subjective digestive responses were also measured. Postprandial plasma AA was similar between WC and WG, while AA appearance was suppressed with HC. Following HC, there was a negative incremental AUC in plasma branched-chain AAs. Further, HC had delayed gastric emptying, increased transit time, and led to exaggerated insulin and GLP-1 responses, in comparison to whole protein formulas. Overall, WC and WG had similar protein and digestive responses with no differences in digestive comfort. Contrastingly, HC led to delayed gastric emptying, attenuated AA appearance, and a heightened circulating insulin response.
Publisher: MDPI AG
Date: 20-07-2018
DOI: 10.3390/NU10070935
Abstract: There is an ongoing debate as to the optimal protein intake in older adults. An increasing body of experimental studies on skeletal muscle protein metabolism as well as epidemiological data suggest that protein requirements with ageing might be greater than many current dietary recommendations. Importantly, none of the intervention studies in this context specifically investigated very old in iduals. Data on the fastest growing age group of the oldest old (aged 85 years and older) is very limited. In this review, we examine the current evidence on protein intake for preserving muscle mass, strength and function in older in iduals, with emphasis on data in the very old. Available observational data suggest beneficial effects of a higher protein intake with physical function in the oldest old. Whilst, studies estimating protein requirements in old and very old in iduals based on whole-body measurements, show no differences between these sub-populations of elderly. However, small s le sizes preclude drawing firm conclusions. Experimental studies that compared muscle protein synthetic (MPS) responses to protein ingestion in young and old adults suggest that a higher relative protein intake is required to maximally stimulate skeletal muscle MPS in the aged. Although, data on MPS responses to protein ingestion in the oldest old are currently lacking. Collectively, the data reviewed for this article support the concept that there is a close interaction of physical activity, diet, function and ageing. An attractive hypothesis is that regular physical activity may preserve and even enhance the responsiveness of ageing skeletal muscle to protein intake, until very advanced age. More research involving study participants particularly aged ≥85 years is warranted to better investigate and determine protein requirements in this specific growing population group.
Publisher: American Physiological Society
Date: 06-2018
DOI: 10.1152/AJPREGU.00421.2017
Abstract: Resistance training (RT) increases muscle fiber size and induces angiogenesis to maintain capillary density. Cold water immersion (CWI), a common postexercise recovery modality, may improve acute recovery, but it attenuates muscle hypertrophy compared with active recovery (ACT). It is unknown if CWI following RT alters muscle fiber type expression or angiogenesis. Twenty-one men strength trained for 12 wk, with either 10 min of CWI ( n = 11) or ACT ( n = 10) performed following each session. Vastus lateralis biopsies were collected at rest before and after training. Type IIx myofiber percent decreased ( P = 0.013) and type IIa myofiber percent increased with training ( P = 0.012), with no difference between groups. The number of capillaries per fiber increased from pretraining in the CWI group ( P = 0.004) but not the ACT group ( P = 0.955). Expression of myosin heavy chain genes ( MYH1 and MYH2), encoding type IIx and IIa fibers, respectively, decreased in the ACT group, whereas MYH7 (encoding type I fibers) increased in the ACT group versus CWI ( P = 0.004). Myosin heavy chain IIa protein increased with training ( P = 0.012) with no difference between groups. The proangiogenic vascular endothelial growth factor protein decreased posttraining in the ACT group versus CWI ( P 0.001), whereas antiangiogenic Sprouty-related, EVH1 domain-containing protein 1 protein increased with training in both groups ( P = 0.015). Expression of microRNAs that regulate muscle fiber type (miR-208b and -499a) and angiogenesis (miR-15a, -16, and -126) increased only in the ACT group ( P 0.05). CWI recovery after each training session altered the angiogenic and fiber type-specific response to RT through regulation at the levels of microRNA, gene, and protein expression.
Publisher: American Physiological Society
Date: 07-2007
DOI: 10.1152/JAPPLPHYSIOL.00236.2006
Abstract: The Na + -K + -ATPase enzyme is vital in skeletal muscle function. We investigated the effects of acute high-intensity interval exercise, before and following high-intensity training (HIT), on muscle Na + -K + -ATPase maximal activity, content, and isoform mRNA expression and protein abundance. Twelve endurance-trained athletes were tested at baseline, pretrain, and after 3 wk of HIT (posttrain), which comprised seven sessions of 8 × 5-min interval cycling at 80% peak power output. Vastus lateralis muscle was biopsied at rest (baseline) and both at rest and immediately postexercise during the first (pretrain) and seventh (posttrain) training sessions. Muscle was analyzed for Na + -K + -ATPase maximal activity (3- O-MFPase), content ([ 3 H]ouabain binding), isoform mRNA expression (RT-PCR), and protein abundance (Western blotting). All baseline-to-pretrain measures were stable. Pretrain, acute exercise decreased 3- O-MFPase activity [12.7% (SD 5.1), P 0.05], increased α 1 , α 2 , and α 3 mRNA expression (1.4-, 2.8-, and 3.4-fold, respectively, P 0.05) with unchanged β-isoform mRNA or protein abundance of any isoform. In resting muscle, HIT increased ( P 0.05) 3- O-MFPase activity by 5.5% (SD 2.9), and α 3 and β 3 mRNA expression by 3.0- and 0.5-fold, respectively, with unchanged Na + -K + -ATPase content or isoform protein abundance. Posttrain, the acute exercise induced decline in 3- O-MFPase activity and increase in α 1 and α 3 mRNA each persisted ( P 0.05) the postexercise 3- O-MFPase activity was also higher after HIT ( P 0.05). Thus HIT augmented Na + -K + -ATPase maximal activity despite unchanged total content and isoform protein abundance. Elevated Na + -K + -ATPase activity postexercise may contribute to reduced fatigue after training. The Na + -K + -ATPase mRNA response to interval exercise of increased α- but not β-mRNA was largely preserved posttrain, suggesting a functional role of α mRNA upregulation.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.CLNU.2018.06.980
Abstract: Human milk (HM) contains a wide array of non-nutritive bioactive elements, including glucocorticoid hormones (glucocorticoid cortisol and cortisone). The relationship between milk-borne glucocorticoids, measures of maternal health and patterns of breast-feeding is not yet established. This study was conducted to determine the influence of maternal and infant related biological and socio-demographic factors on the levels of glucocorticoids hormones in HM. S les were obtained from lactating mothers (n = 656) participating in the Finnish cohort the STEPS study (Steps to the Healthy Development and Well-being of Children) when the infants were 11.29 (±2.6) weeks of age. Glucocorticoids (both cortisol and cortisone) concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Maternal demographics, biological and social factors were obtained using hospital records and self-reported diaries and questionnaires. The majority of women reported that they were exclusively breastfeeding at the time of s le donation (51.2%). For all collected s les, cortisone (9.55 ± 3.44 ng/ml) was the predominant hormone and cortisol (7.39 ± 5.97 ng/ml) was present in all s les. Strong and positive correlation was found between cortisol and cortisone (r = 0.60, p=<0.0001). Cortisone was statistically different between overweight, normal and underweight women (p = 0.01) for cortisol no difference was seen (p = 0.96). Whilst, preterm birth (born before 37 week gestation) was positively associated with both cortisol (p = 0.04) and cortisone (p = 0.01). There was also a significant but weaker negative relationship between mothers educational status and cortisol (p = 0.05) and no effect was seen for cortisone (p = 0.82). Interestingly, no significant differences was found in glucocorticoid concentrations between exclusive and partial breastfeeding women. HM contains glucocorticoids hormones. The concentrations are influenced by the varying maternal factors including maternal weight, preterm birth and maternal educational status, suggesting the possible role of maternal biological and social influences on milk hormonal composition. Interestingly, there was no influence of feeding patterns on HM glucocorticoids. Further analysis is required to fully explore the relationship with measures of maternal stress, including mother's glucocorticoid status.
Publisher: Human Kinetics
Date: 11-2019
Abstract: Purpose : To determine the acute effects of carbohydrate (CHO) ingestion following a bout of maximal eccentric resistance exercise on key anabolic kinases of mammalian target of rapamycin and extracellular signal-regulated kinase (ERK) pathways. The authors’ hypothesis was that the activation of anabolic signaling pathways known to be upregulated by resistance exercise would be further stimulated by the physiological hyperinsulinemia resulting from CHO supplementation. Methods : Ten resistance-trained men were randomized in a crossover, double-blind, placebo (PLA)-controlled manner to ingest either a noncaloric PLA or 3 g/kg of CHO beverage throughout recovery from resistance exercise. Muscle biopsies were collected at rest, immediately after a single bout of intense lower body resistance exercise, and after 3 hr of recovery. Results : CHO ingestion elevated plasma glucose and insulin concentrations throughout recovery compared with PLA ingestion. The ERK pathway (phosphorylation of ERK1/2 [Thr202/Tyr204], RSK [Ser380], and p70S6K [Thr421/Ser424]) was markedly activated immediately after resistance exercise, without any effect of CHO supplementation. The phosphorylation state of AKT (Thr308) was unchanged postexercise in the PLA trial and increased at 3 hr of recovery above resting with ingestion of CHO compared with PLA. Despite stimulating-marked phosphorylation of AKT, CHO ingestion did not enhance resistance exercise–induced phosphorylation of p70S6K (Thr389) and rpS6 (Ser235/236 and Ser240/244). Conclusion : CHO supplementation after resistance exercise and hyperinsulinemia does not influence the ERK pathway nor the mTORC1 target p70S6K and its downstream proteins, despite the increased AKT phosphorylation.
Publisher: Springer Science and Business Media LLC
Date: 17-07-2017
DOI: 10.1038/S41598-017-05793-0
Abstract: We examined whether maternal fish oil supplementation during pregnancy could prevent development of insulin resistance in adult male offspring of rat dams fed a high-fat diet. Time-mated Sprague-Dawley rat dams were randomised into four treatment groups: Con-Con, dams fed a control diet (fat: 15% kcal) and administered water by gavage Con-FO, control diet with unoxidised fish oil by gavage HF-Con, high-fat diet (fat: 45% kcal) and water by gavage and HF-FO, high-fat diet and unoxidised fish oil by gavage. Dams were fed the allocated diet ad libitum during pregnancy and lactation, but daily gavage occurred only during pregnancy. After weaning, male offspring consumed a chow diet ad libitum until adulthood. Maternal high-fat diet led to increased food consumption, adiposity, systolic blood pressure, and triglycerides and plasma leptin in adult HF-Con offspring. HF-Con offspring also exhibited lower insulin sensitivity than Con-Con rats. Male offspring from HF-FO group were similar to HF-Con regarding food consumption and most metabolic parameters. However, insulin sensitivity in the HF-FO group was improved relative to the HF-Con offspring. Supplementation with unoxidised n-3 PUFA rich oils in the setting of a maternal obesogenic diet improved insulin sensitivity, but had no impact on body composition of adult male offspring.
Publisher: Impact Journals, LLC
Date: 17-03-2020
Publisher: American Diabetes Association
Date: 04-2003
DOI: 10.2337/DIABETES.52.4.926
Abstract: An acute bout of exercise increases skeletal muscle glucose uptake, improves glucose homeostasis and insulin sensitivity, and enhances muscle oxidative capacity. Recent studies have shown an association between these adaptations and the energy-sensing 5′ AMP-activated protein kinase (AMPK), the activity of which is increased in response to exercise. Activation of AMPK has been associated with enhanced expression of key metabolic proteins such as GLUT-4, hexokinase II (HKII), and mitochondrial enzymes, similar to exercise. It has been hypothesized that AMPK might regulate gene and protein expression through direct interaction with the nucleus. The purpose of this study was to determine if nuclear AMPK α2 content in human skeletal muscle was increased by exercise. Following 60 min of cycling at 72 ± 1% of Vo2peak in six male volunteers (20.6 ± 2.1 years 72.9 ± 2.1 kg Vo2peak = 3.62 ± 0.18 l/min), nuclear AMPK α2 content was increased 1.9 ± 0.4-fold (P = 0.024). There was no change in whole-cell AMPK α2 content or AMPK α2 mRNA abundance. These results suggest that nuclear translocation of AMPK might mediate the effects of exercise on skeletal muscle gene and protein expression.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2012
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Wiley
Date: 03-11-2012
DOI: 10.1007/S11745-012-3735-5
Abstract: Using lipidomic methodologies the impact that meal lipid composition and metabolic syndrome (MetS) exerts on the postprandial chylomicron triacylglycerol (TAG) response was examined. Males (9 control 11 MetS) participated in a randomised crossover trial ingesting two high fat breakfast meals composed of either dairy-based foods or vegetable oil-based foods. The postprandial lipidomic molecular composition of the TAG in the chylomicron-rich (CM) fraction was analysed with tandem mass spectrometry coupled with liquid chromatography to profile CM TAG species and targeted TAG regioisomers. Postprandial CM TAG concentrations were significantly lower after the dairy-based foods compared with the vegetable oil-based foods for both control and MetS subjects. The CM TAG response to the ingested meals involved both significant and differential depletion of TAG species containing shorter- and medium-chain fatty acids (FA) and enrichment of TAG molecular species containing C16 and C18 saturated, monounsaturated and diunsaturated FA. Furthermore, there were significant changes in the TAG species between the food TAG and CM TAG and between the 3- and 5-h postprandial s les for the CM TAG regioisomers. Unexpectedly, the postprandial CM TAG concentration and CM TAG lipidomic responses did not differ between the control and MetS subjects. Lipidomic analysing of CM TAG molecular species revealed dynamic changes in the molecular species of CM TAG during the postprandial phase suggesting either preferential CM TAG species formation and/or clearance.
Publisher: Springer Science and Business Media LLC
Date: 16-12-2008
Publisher: Wiley
Date: 02-09-2020
DOI: 10.1002/JBM4.10399
Publisher: Wiley
Date: 13-08-2015
DOI: 10.1113/JP270570
Publisher: Cambridge University Press (CUP)
Date: 04-08-2010
DOI: 10.1017/S0007114509991334
Abstract: The metabolic fate of dietary n -3 docosapentaenoic acid (DPA) in mammals is currently unknown. The aim of the present study was to determine the extent of conversion of dietary DPA to DHA and EPA in rats. Four groups of male weanling Sprague–Dawley rats (aged 5 weeks) were given 50 mg of DPA, EPA, DHA or oleic acid, daily for 7 d by gavage. At the end of the treatment period, the tissues were analysed for concentrations of long-chain PUFA. DPA supplementation led to significant increases in DPA concentration in all tissues, with largest increase being in adipose (5-fold) and smallest increase being in brain (1·1-fold). DPA supplementation significantly increased the concentration of DHA in liver and the concentration of EPA in liver, heart and skeletal muscle, presumably by the process of retroconversion. EPA supplementation significantly increased the concentration of EPA and DPA in liver, heart and skeletal muscle and the DHA concentration in liver. DHA supplementation elevated the DHA levels in all tissues and EPA levels in the liver. Adipose was the main tissue site for accumulation of DPA, EPA and DHA. These data suggest that dietary DPA can be converted to DHA in the liver, in a short-term study, and that in addition it is partly retroconverted to EPA in liver, adipose, heart and skeletal muscle. Future studies should examine the physiological effect of DPA in tissues such as liver and heart.
Publisher: American Physiological Society
Date: 06-2004
DOI: 10.1152/JAPPLPHYSIOL.01318.2003
Abstract: Fasting forces adaptive changes in whole body and skeletal muscle metabolism that increase fat oxidation and decrease the oxidation of carbohydrate. We tested the hypothesis that 40 h of fasting would decrease pyruvate dehydrogenase (PDH) activity and increase PDH kinase (PDK) isoform mRNA expression in human skeletal muscle. The putative transcriptional activators of PDK isozymes, peroxisome proliferator-activated receptor-α (PPAR-α) protein, and forkhead homolog in rhabdomyosarcoma (FKHR) mRNA were also measured. Eleven healthy adults fasted after a standard meal (25% fat, 60% carbohydrate, 15% protein) with blood and skeletal muscle s les taken at 3, 15, and 40 h postprandial. Fasting increased plasma free fatty acid, glycerol, and β-hydroxybutyrate concentrations and decreased glucose and insulin concentrations. PDH activity decreased from 0.88 ± 0.11 mmol acetyl-CoA · min -1 · kg wet muscle wt -1 at 3 h to 0.62 ± 0.10 ( P = not significant) and 0.39 ± 0.06 ( P 0.05) mmol · min -1 · kg wet mass -1 after 15 and 40 h of fasting. Although all four PDK isoforms were expressed in human skeletal muscle, PDK-2 and -4 mRNA were the most abundant. PDK-1 and -3 mRNA abundance was ∼1 and 15% of the PDK-2 and -4 levels, respectively. The 40-h fast had no effect on PDK-1, -2, and -3 mRNA expression. PDK-4 mRNA was significantly increased ∼3-fold after 15 h and ∼14-fold after 40 h of fasting. Skeletal muscle PPAR-α protein and FKHR mRNA abundance were unaffected by the fast. The results suggest that decreased PDH activation after 40 h of fasting may have been a function of the large increase in PDK-4 mRNA expression and possible subsequent increase in PDK protein and activity. The changes in PDK-4 expression and PDH activity did not coincide with increases in the transcriptional activators PPAR-α and FKHR.
Publisher: Informa UK Limited
Date: 19-11-2018
Publisher: American Diabetes Association
Date: 06-2007
DOI: 10.2337/DB06-1398
Abstract: A single bout of aerobic exercise can enhance insulin action, but whether a similar effect occurs after resistance exercise is unknown. Hyperinsulinemic-euglycemic cl s were performed on eight male subjects at rest and after a single bout and three repeated bouts of resistance exercise over 7 days. Skeletal muscle biopsies were taken before and after the cl and immediately after a single exercise bout. Whole-body insulin action measured by glucose infusion rate decreased (P & 0.05) after a single exercise bout, whereas in response to repeated bouts of resistance exercise, the glucose infusion rate was similar to the rest trial. In skeletal muscle, Akt substrate of 160 kDa (AS160) phosphorylation, an Akt substrate implicated in the regulation of GLUT4 translocation, and its interaction with 14-3-3 was decreased (P & 0.05) only after a single exercise bout. Insulin increased (P & 0.05) phosphorylation of AS160 and its interaction with 14-3-3, but the insulin response was not influenced by resistance exercise. Phosphorylation of insulin receptor substrate-1 and Akt were similar to changes in AS160 phosphorylation after exercise and/or insulin. In conclusion, a single bout of resistance exercise impairs whole-body insulin action. Regulation of AS160 and interaction with 14-3-3 in skeletal muscle are influenced by resistance exercise and insulin but do not fully explain the effect of resistance exercise on whole-body insulin action.
Publisher: Wiley
Date: 04-2019
Abstract: MicroRNA are critical to the coordinated post-transcriptional regulation of gene expression, yet few studies have addressed the influence of habitual diet on microRNA expression. High protein diets impact cardiometabolic health and body composition in the elderly suggesting the possibility of a complex systems response. Therefore, high-throughput small RNA sequencing technology is applied in response to doubling the protein recommended dietary allowance (RDA) over 10 weeks in older men to examine alterations in circulating miRNAome. Older men (n = 31 74.1 ± 0.6 y) are randomized to consume either RDA (0.8 g kg The study findings suggest a possible selective alteration in the post-transcriptional regulation of the immune system following a high protein diet. However, very few microRNAs are altered despite a large change in the dietary protein.
Publisher: Wiley
Date: 29-09-2011
DOI: 10.1111/J.1748-1716.2011.02344.X
Abstract: Production of reactive oxygen species (ROS) in skeletal muscle is markedly increased during exercise and may be essential for exercise adaptation. We, therefore, investigated the effects of infusion with the antioxidant N-acetylcysteine (NAC) on exercise-induced activation of signalling pathways and genes involved in exercise adaptation in human skeletal muscle. Subjects completed two exercise tests, 7 days apart, with saline (control, CON) or NAC infusion before and during exercise. Exercise tests comprised of cycling at 71% VO(2peak) for 45 min, and then 92% VO(2peak) to fatigue, with vastus lateralis biopsies at pre-infusion, after 45-min cycling and at fatigue. Analysis was conducted on the mitogen-activated protein kinase signalling pathways, demonstrating that NAC infusion blocked the exercise-induced increase in JNK phosphorylation, but not ERK1/2, or p38 MAPK. Nuclear factor-κB p65 phosphorylation was unaffected by exercise however, it was reduced in NAC at fatigue by 14% (P < 0.05) compared with pre-infusion. Analysis of exercise and/or ROS-sensitive genes demonstrated that exercise-induced mRNA expression is ROS dependent of MnSOD, but not PGC-1α, interleukin-6, monocyte chemotactic protein-1, or heat-shock protein 70. These results suggest that inhibition of ROS attenuates some skeletal muscle cell signalling pathways and gene expression involved in adaptations to exercise.
Publisher: Wiley
Date: 12-2017
DOI: 10.14814/PHY2.13526
Publisher: Cambridge University Press (CUP)
Date: 2020
DOI: 10.1017/JNS.2020.15
Abstract: Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 ( sd 3⋅6) years n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal s les were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA licon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
Publisher: Frontiers Media SA
Date: 05-11-2020
Publisher: Elsevier BV
Date: 09-2016
Publisher: MDPI AG
Date: 02-03-2021
DOI: 10.3390/NU13030821
Abstract: Scope: B vitamers are co-enzymes involved in key physiological processes including energy production, one-carbon, and macronutrient metabolism. Studies profiling B vitamers simultaneously in parent–child dyads are scarce. Profiling B vitamers in parent–child dyads enables an insightful determination of gene–environment contributions to their circulating concentrations. We aimed to characterise: (a) parent–child dyad concordance, (b) generation (children versus adults), (c) age (within the adult subgroup (age range 28–71 years)) and (d) sex differences in plasma B vitamer concentrations in the CheckPoint study of Australian children. Methods and Results: 1166 children (11 ± 0.5 years, 51% female) and 1324 parents (44 ± 5.1 years, 87% female) took part in a biomedical assessment of a population-derived longitudinal cohort study: The Growing Up in Australia’s Child Health CheckPoint. B vitamer levels were quantified by UHPLC/MS-MS. B vitamer levels were weakly concordant between parent–child pairs (10–31% of variability explained). All B vitamer concentrations exhibited generation-specificity, except for flavin mononucleotide (FMN). The levels of thiamine, pantothenic acid, and 4-pyridoxic acid were higher in male children, and those of pantothenic acid were higher in male adults compared to their female counterparts. Conclusion: Family, age, and sex contribute to variations in the concentrations of plasma B vitamers in Australian children and adults.
Publisher: American Physiological Society
Date: 06-2018
DOI: 10.1152/PHYSIOLGENOMICS.00112.2017
Abstract: The loss of muscle size, strength, and quality with aging is a major determinant of morbidity and mortality in the elderly. The regulatory pathways that impact the muscle phenotype include the translational regulation maintained by microRNAs (miRNA). Yet the miRNAs that are expressed in human skeletal muscle and relationship to muscle size, strength, and quality are unknown. Using next-generation sequencing, we selected the 50 most abundantly expressed miRNAs and then analyzed them in vastus lateralis muscle, obtained by biopsy from middle-aged males ( n = 48 50.0 ± 4.3 yr). Isokinetic strength testing and midthigh computed tomography was undertaken for muscle phenotype analysis. Muscle attenuation was measured by computerized tomography and is inversely proportional to myofiber lipid content. miR-486-5p accounted for 21% of total miR sequence reads, with miR-10b-5p, miR-133a-3p, and miR-22-3p accounting for a further 15, 12, and 10%, respectively. Isokinetic knee extension strength and muscle cross-sectional area were positively correlated with miR-100-5p, miR-99b-5p, and miR-191-5p expression. Muscle attenuation was negatively correlated to let-7f-5p, miR-30d-5p, and miR-125b-5p expression. In silico analysis implicates miRNAs related to strength and muscle size in the regulation of mammalian target of rapamycin, while miRNAs related to muscle attenuation may have potential roles regulating the transforming growth factor-β/SMAD3 pathway.
Publisher: American Physiological Society
Date: 04-2018
DOI: 10.1152/JAPPLPHYSIOL.01100.2017
Abstract: Arachidonic acid (ARA), a polyunsaturated ω-6 fatty acid, acts as precursor to a number of prostaglandins with potential roles in muscle anabolism. It was hypothesized that ARA supplementation might enhance the early anabolic response to resistance exercise (RE) by increasing muscle protein synthesis (MPS) via mammalian target of rapamycin (mTOR) pathway activation and/or the late anabolic response by modulating ribosome biogenesis and satellite cell expansion. Nineteen men with ≥1 yr of resistance-training experience were randomized to consume either 1.5 g daily ARA or a corn-soy-oil placebo in a double-blind manner for 4 wk. Participants then undertook fasted RE (8 sets each of leg press and extension at 80% 1-repetition maximum), with vastus lateralis biopsies obtained before exercise, immediately postexercise, and at 2, 4, and 48 h of recovery. MPS (measured via stable isotope infusion) was not different between groups ( P = 0.212) over the 4-h recovery period. mTOR pathway members p70 S6 kinase and S6 ribosomal protein were phosphorylated postexercise ( P 0.05), with no difference between groups. 45S preribosomal RNA increased 48 h after exercise only in ARA ( P = 0.012). Neural cell adhesion molecule-positive satellite cells per fiber increased 48 h after exercise ( P = 0.013), with no difference between groups ( P = 0.331). Prior ARA supplementation did not alter the acute anabolic response to RE in previously resistance-trained men however, at 48 h of recovery, ribosome biogenesis was stimulated only in the ARA group. The findings do not support a mechanistic link between ARA and short-term anabolism, but ARA supplementation in conjunction with resistance training may stimulate increases in translational capacity. NEW & NOTEWORTHY Four weeks of daily arachidonic acid supplementation in trained men did not alter their acute muscle protein synthetic or anabolic signaling response to resistance exercise. However, 48 h after exercise, men supplemented with arachidonic acid showed greater ribosome biogenesis and a trend toward greater change in satellite cell content. Chronic arachidonic acid supplementation does not appear to regulate the acute anabolic response to resistance exercise but may augment muscle adaptation in the following days of recovery.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1093/AJCN/NQZ279
Abstract: Lactose malabsorption (LM) is a major cause of digestive discomfort from dairy products. Recently, a role for bovine β-casein A1 has been proposed. We examined whether there are distinct symptoms of digestive discomfort due to either lactose or differing bovine β-casein types. Women (n = 40 age: 25.2 ± 0.5 y) with self-reported varying dairy tolerance underwent a 50-g lactose challenge. Based on postchallenge LM and digestive discomfort, participants were classified as either lactose intolerant (LI n = 10, self-reported intolerant, diagnosed lactose intolerant), nonlactose dairy intolerant (NLDI n = 20, self-reported intolerant, diagnosed lactose tolerant), or dairy tolerant (DT n = 10, self-reported tolerant, diagnosed lactose tolerant). In a double-blinded randomized sequence, participants consumed 750 mL conventional milk (CON containing A1 and A2 β-casein and lactose), a2 Milk (A2M exclusively containing A2 β-casein with lactose), or lactose-free conventional milk (LF-CON containing A1 and A2 β-casein without lactose). Subjective digestive symptoms and breath hydrogen (measuring LM) were recorded regularly over 3 h, and further ad hoc digestive symptoms over 12 h. LI subjects experienced prolonged digestive discomfort with CON milk. A2M reduced (P < 0.05) some symptoms (nausea: A2M 8 ± 3 mm compared with CON 15 ± 3mm fecal urgency: A2M 4 ± 1 compared with CON 10 ± 3 mm), and attenuated the rise in breath hydrogen over 3 h, relative to CON milk (A2M 59 ± 23 compared with CON 98 ± 25 ppm at 150 min P < 0.01). In contrast, NLDI subjects experienced rapid-onset, transient symptoms (abdominal distension, bloating, and flatulence) without increased breath hydrogen, irrespective of milk type. In LI in iduals, LM and digestive comfort with lactose-containing milks was improved with milk containing exclusively A2 β-casein. Furthermore, self-reported dairy intolerance without LM (NLDI) is characterized by early-onset digestive discomfort following milk ingestion, irrespective of lactose content or β-casein type. This trial was registered at www.anzctr.org.au as ACTRN12616001694404.
Publisher: MDPI AG
Date: 21-10-2015
DOI: 10.3390/NU7105420
Publisher: Springer Science and Business Media LLC
Date: 03-2004
DOI: 10.1007/S00125-003-1322-2
Abstract: Recruitment of the protein c-Cbl to the insulin receptor (IR) and its tyrosine phosphorylation via a pathway that is independent from phosphatidylinositol 3'-kinase is necessary for insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. The activation of this pathway by insulin or exercise has yet to be reported in skeletal muscle. Lean and obese Zucker rats were randomly assigned to one of three treatment groups: (i). control, (ii). insulin-stimulated or (iii). acute, exhaustive exercise. Hind limb skeletal muscle was removed and the phosphorylation state of IR, Akt and c-Cbl measured. Insulin receptor phosphorylation was increased 12-fold after insulin stimulation ( p<0.0001) in lean rats and threefold in obese rats. Acute exercise had no effect on IR tyrosine phosphorylation. Similar results were found for serine phosphorylation of Akt. Exercise did not alter c-Cbl tyrosine phosphorylation in skeletal muscle of lean or obese rats. However, in contrast to previous studies in adipocytes, c-Cbl tyrosine phosphorylation was reduced after insulin treatment ( p<0.001). We also found that c-Cbl associating protein expression is relatively low in skeletal muscle of Zucker rats compared to 3T3-L1 adipocytes and this could account for the reduced c-Cbl tyrosine phosphorylation after insulin treatment. Interestingly, basal levels of c-Cbl tyrosine phosphorylation were higher in skeletal muscle from insulin-resistant Zucker rats ( p<0.05), but the physiological relevance is not clear. We conclude that the regulation of c-Cbl phosphorylation in skeletal muscle differs from that previously reported in adipocytes.
Publisher: Wiley
Date: 03-2013
DOI: 10.1002/OBY.20070
Abstract: The molecular mechanisms underpinning the loss of skeletal muscle mass and strength associated with insulin resistance remain to be extensively investigated. There is mounting recognition that certain ligands of the transforming growth factor (TGF)-β family are upregulated in insulin resistant states, including obesity. This study analyses the expression of potent ligands of this family, TGF-β1 and myostatin (MSTN) and downstream components of the canonical TGF-β family signaling pathway (Smads) in skeletal muscle from lean and insulin resistant obese subjects. Biopsies taken from the rectus abdominis muscle of lean (n = 13) and obese subjects (n = 20) were analyzed for the expression of TGF-β1 and MSTN as well as TGF-β signaling components, Smad2, 3, and 4, and transcription of the muscle regulatory factors (MRFs), MyoD and myogenin. Increases in Smad2 and Smad3 phosphorylation, Smad4 and total Smad3 were observed to be coincident with altered transcription of MyoD and myogenin. TGF-β1 and MSTN protein levels were not significantly altered. Thus, increased Smad signaling is likely to account for, at least, a proportion of obesity and insulin resistance-related muscle atrophy through reduced MRF, particularly MyoD, transcription. The major regulatory ligand may not be MSTN and further members of the TGF-β1 superfamily should be considered.
Publisher: Frontiers Media SA
Date: 15-02-2021
Abstract: Background: Sheep milk (SM) is a possible alternate dairy source for those who experience digestive symptoms with cow milk (CM). While both the milks contain lactose, one of the causes for self-reported intolerance to CM, the composition of SM and CM also differs across proteins and fats, which have been shown to impact digestive processes. Objective: To compare the acute digestive comfort and lactose malabsorption of SM to CM in female dairy avoiders. Method: In a double-blinded, randomized cross over trial, 30 dairy-avoiding females (aged 20–30 years) drank 650 mL of SM or CM (each reconstituted from spray dried powder) following an overnight fast, on two separate occasions at least 1 week apart. Blood s les were collected for glucose and insulin assessment, and single nucleotide polymorphisms of the lactase ( LCT ) gene (C/T 13910 and G/A 22018 ). Breath H 2 and visual analog scale (VAS) digestive symptom scores were recorded at fasting and regular intervals over 4 h after ingestion. Results: Eighty percentage of study participants were lactase non-persistent (LNP CC 13910 and GG 22018 genotype). Digestive symptoms, including abdominal cr s, distension, rumbling, bloating, belching, diarrhea, flatulence, vomiting, and nausea, were similar in response to SM and CM ingestion (milk × time, P & 0.05). Breath H 2 was greater after CM than SM (72 ± 10 vs. 43 ± 6 ppm at 240 min, P & 0.001), which may be due to greater lactose content in CM (33 vs. 25 g). Accordingly, when corrected for the lactose content breath H 2 did not differ between the two milks. The response remained similar when analyzed in the LNP subset alone ( n = 20). Conclusions: Despite a higher energy and nutrient content, SM did not increase adverse digestive symptoms after ingestion, relative to CM, although there was a reduced breath H 2 response, which could be attributed to the lower lactose content in SM. The tolerability of SM should be explored in populations without lactose intolerance for whom underlying trigger for intolerance is unknown.
Publisher: Wiley
Date: 27-02-2018
Abstract: Limb immobilization results in a rapid loss of muscle size and strength. The resultant alterations in signaling pathways governing myogenesis, catabolism, and mitochondrial biogenesis are likely to include posttranscriptional regulation mediated by altered microRNAs (miRNAs). Given that protein ingestion exerts an anabolic action and may act as a countermeasure to mitigate muscle loss with immobilization, it is important to examine miRNA in this context. The objective of the study is therefore to characterize the vastus lateralis miRNA response to 14 days of disuse in males (45-60 years) randomized to receive supplementation with 20 g d
Publisher: Springer Science and Business Media LLC
Date: 29-06-2020
DOI: 10.1186/S12876-020-01352-6
Abstract: Adult lactase non-persistence (LNP) is due to low lactase expression, resulting in lactose malabsorption (LM). LNP is a genetic trait, but is typically determined by LM markers including breath H 2 , blood glucose, and urinary galactose after a lactose tolerance test. Known validity of these markers using milk is limited, despite being common practice. Compositional variation, such as β-casein variants, in milk may impact diagnostic efficacy. This study aimed to evaluate the diagnostic accuracy to detect LNP using these commonly measured LM markers after both lactose and milk challenges. Fourty healthy young women were challenged with 50 g lactose then randomized for separate cross-over visits to ingest 750 mL milk (37.5 g lactose) as conventional (both A1 and A2 β-casein) and A1 β-casein-free (a2 Milk™) milk. Blood, breath and urine were collected prior to and up to 3 h following each challenge. The presence of C/T 13910 and G/A 22018 polymorphisms, determined by restriction fragment length polymorphism, was used as the diagnostic reference for LNP. Genetic testing identified 14 out of 40 subjects as having LNP (C/C 13910 and G/G 22018 ). All three LM markers (breath H 2 , plasma glucose and urinary galactose/creatinine) discriminated between lactase persistence (LP) and LNP following lactose challenge with an area under the receiver operating characteristic (ROC) curve (AUC) of 1.00, 0.75 and 0.73, respectively. Plasma glucose and urinary galactose/creatinine were unreliable (AUC 0.70) after milk ingestion. The specificity of breath H 2 remained high (100%) when milk was used, but sensitivity was reduced with conventional (92.9%) and a2 Milk™ (78.6%) compared to lactose (sensitivities adjusted for lactose content). The breath H 2 optimal cut-off value was lower with a2 Milk™ (13 ppm) than conventional milk (21 ppm). Using existing literature cut-off values the sensitivity and specificity of breath H 2 was greater than plasma glucose to detect LNP following lactose challenge whereas values obtained for urinary galactose/creatinine were lower than the existing literature cut-offs. This study showed accurate diagnosis of LNP by breath H 2 irrespective of the substrate used, although the diagnostic threshold may vary depending on the lactose substrate or the composition of the milk. ACTRN12616001694404 . Registered prospectively on December 9, 2016.
Publisher: Springer Science and Business Media LLC
Date: 14-10-2015
DOI: 10.1007/S00394-014-0780-2
Abstract: To investigate the mechanisms of impairments in oxidative metabolism in obese and diabetic (T2DM) skeletal muscle, this study analysed the adaptive expression of genes involved in fatty acid (FA) oxidation and mitochondrial biogenesis in primary myotubes treated with elevated FAs. Muscle s les from obese or obese T2DM donors were stored or processed into human primary skeletal muscle myotubes, which were treated for 6 h with a saturated (palmitic acid) or a monounsaturated (oleic acid) FA with or without a polyunsaturated FA (eicosapentaenoic acid: EPA). Real-time PCR analysis was used to determine mRNA expression. Basal pyruvate dehydrogenase kinase 4 (PDK4) mRNA expression in whole muscle s les from obese and T2DM subjects was increased compared to lean (P < 0.05 n = 13-20/group). In obese- and T2DM-derived myotubes, oleic acid treatment alone and in combination with EPA increased PDK4 mRNA expression compared to control (P < 0.05 n = 7/group), whereas palmitic acid alone and in combination with EPA only increased PDK4 mRNA in T2DM-derived myotubes compared to control (P < 0.05 n = 7/group). EPA alone did not alter mRNA expression of PDK4. These findings show that FAs induce the expression of PDK4 mRNA, which was increased in myotubes cultured from obese and T2DM donors. This persistent difference in PDK4 expression, present after culturing, suggests a fundamental alteration in the FA-mediated gene expression. This may in turn translate to differences in the regulation of oxidative substrate flux to impact on insulin sensitivity.
Publisher: Wiley
Date: 04-2004
Publisher: MDPI AG
Date: 16-11-2021
DOI: 10.3390/DIAGNOSTICS11112127
Abstract: Central fat accumulation is a significant determinant of cardio-metabolic health risk, known to differ between ethnically distinct human populations. Despite evidence for preferential central adiposity in Asian populations, the proportional distribution between the subcutaneous and visceral compartments in Chinese postmenopausal women has not been thoroughly investigated. For this analysis, volumetrically quantified subcutaneous and visceral adipose tissue (SAT, VAT) in the pelvic and abdominal regions of postmenopausal Asian (Chinese-Singaporean) and Caucasian (German) women matched for age and Body Mass Index (BMI) was undertaken, to examine such differences between the two groups. Volumes were calculated from segmentations of magnetic resonance imaging datasets of the abdomen and pelvis. Despite SAT, VAT, and the corresponding total adipose tissue (TAT) being similar between the groups, VAT/SAT and VAT/TAT were higher in the Asian group (by 24.5% and 18.2%, respectively, each p = 0.02). Further, VAT/SAT and VAT/TAT were positively correlated with BMI in the Caucasian group only (p = 0.02 and p = 0.01, respectively). We concluded that VAT is proportionally higher in the non-obese Asian women, compared to the Caucasian women of matched age and BMI. This conclusion is in agreement with existing literature showing higher abdominal adiposity in Asian populations. Additionally, in the Asian group, BMI did not correlate with visceral adiposity on a significant level. Further analysis is required to examine the extent to which this increased VAT may impact cardio-metabolic health. There is, however, a need to emphasize healthy lifestyle behaviors in non-obese post-menopausal women of Chinese ancestry.
Publisher: Springer Science and Business Media LLC
Date: 28-02-2019
DOI: 10.1007/S12603-019-1171-4
Abstract: The mammalian target of rapamycin complex 1 (mTORC1) is fundamental for many cellular processes, yet it is often dysregulated with aging. Increased amino acid (AA) availability is correlated with the expression of AA transporters (AAT) and mTORC1 activity. Although many AA sensors and mediators have been proposed to relay the AA signal to mTORC1, it has not yet been determined if chronic dietary intervention affects the expression of AAT, sensors and mediators and their relationships with mTORC1 activity. This study investigated whether the consumption of a diet containing either the current recommended daily allowance (RDA) of protein intake (0.8 g/kg/d) or twice the RDA (2RDA) for ten weeks affected the expression of targets associated with AA transport, sensing and mTORC1 regulation in 26 older men (70-81 years). Muscle biopsies were collected before and after the intervention under fasting conditions. Diets were controlled by providing fully prepared meals and snacks. Western blot and quantitative polymerase chain reaction were used to measure protein and gene expression respectively. Consumption of 2RDA reduced the protein expression of L-type amino acid transporter 1 (LAT1). However, plasma leucine concentration and basal mTORC1 activity were unaltered. The downregulation of LAT1 did not affect the expression of AA sensors and mediators, including leucyl tRNA synthetase (LRS), cytosolic arginine sensor for mTORC1 (CASTOR1), Sestrin2 and Rag proteins. Instead, total ribosomal protein S6 (RPS6) was upregulated with 2RDA. Ten weeks of 2RDA diet did not affect the fasting mTORC1 signaling, but increased total RPS6 might suggest improved muscular translational capacity to maintain muscular mass.
Publisher: MDPI AG
Date: 09-2018
DOI: 10.3390/NU10091194
Abstract: Male and female infants respond differentially to environmental stimuli, with different growth and neurodevelopmental trajectories. Male infants are more likely to be disadvantaged when subjected to adversity and show a higher risk of perinatal complications. However, the underlying causes of this sex-bias are not well defined and optimising the early life nutritional care may be necessary to minimise the “male disadvantage” that may be experienced early in life. Experimental models have demonstrated that animal milk composition differs according to offspring sex, suggesting that the tailoring of early life nutrition may be one mechanism to maximise health protection and development to infants of both sexes. However, evidence for a sex-specificity in human milk composition is limited and conflicting, with studies documenting higher milk energy content for either male or female infants. These data show sex differences, however, there has been limited compositional analysis of the current data nor strategies proposed for how sex-specific compositional differences in early life nutrition may be used to improve infant health. The present narrative review highlights that an improved understanding of sex-specific human milk composition is essential for promoting optimal infant growth and development.
Publisher: Springer Science and Business Media LLC
Date: 08-07-2021
DOI: 10.1007/S00394-021-02607-Y
Abstract: Cardiovascular diseases and cognitive decline, predominant in ageing populations, share common features of dysregulated one-carbon (1C) and cardiometabolic homeostasis. However, few studies have addressed the impact of multifaceted lifestyle interventions in older adults that combine both nutritional supplementation and resistance training on the co-regulation of 1C metabolites and cardiometabolic markers. 95 institutionalised older adults (83 ± 6 years, 88.4% female) were randomised to receive resistance training with or without nutritional supplementation (Fortifit), or cognitive training (control for socialisation) for 6 months. Fasting plasma 1C metabolite concentrations, analysed by liquid chromatography coupled with mass spectrometry, and cardiometabolic parameters were measured at baseline and the 3- and 6-month follow-ups. Regardless of the intervention group, choline was elevated after 3 months, while cysteine and methionine remained elevated after 6 months (mixed model time effects, p 0.05). Elevated dimethylglycine and lower betaine concentrations were correlated with an unfavourable cardiometabolic profile at baseline (spearman correlations, p 0.05). However, increasing choline and dimethylglycine concentrations were associated with improvements in lipid metabolism in those receiving supplementation (regression model interaction, p 0.05). Choline metabolites, including choline, betaine and dimethylglycine, were central to the co-regulation of 1C metabolism and cardiometabolic health in older adults. Metabolites that indicate upregulated betaine-dependent homocysteine remethylation were elevated in those with the greatest cardiometabolic risk at baseline, but associated with improvements in lipid parameters following resistance training with nutritional supplementation. The relevance of how 1C metabolite status might be optimised to protect against cardiometabolic dysregulation requires further attention.
Publisher: MDPI AG
Date: 08-03-2010
DOI: 10.3390/NU2030317
Abstract: We found an error in our paper recently published in Nutrients [1]. [...]
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.CYTO.2011.03.012
Abstract: The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade has been identified as a crucial factor for myogenesis. The STAT3 isoform is essential for satellite cell migration and myogenic differentiation as it mediates the expression of muscle specific myogenic factors. The SOCS (suppressors of cytokine signaling) family of proteins down-regulates STAT activation. Primary human skeletal muscle cells were isolated and cultured to investigate the effect of SOCS3 adenoviral overexpression on myotube maturation. It was demonstrated that STAT3 inhibition did not influence myotube development or survival. Moreover, SOCS3 overexpression enhances the mRNA expression of downstream targets of STAT3, c-FOS and VEGF. These increases were correlated with enhanced mRNA expression of genes associated with muscle maturation and hypertrophy. Thus SOCS3 influences myoblast differentiation and SOCS3 may be significant in regulating the activity of genes previously identified as transcriptionally regulated by STAT3.
Publisher: MDPI AG
Date: 30-04-2018
Publisher: Elsevier BV
Date: 12-2016
Publisher: Wiley
Date: 2016
DOI: 10.14814/PHY2.12670
Publisher: MDPI
Date: 16-12-2019
Publisher: American Physiological Society
Date: 03-2018
DOI: 10.1152/JAPPLPHYSIOL.00397.2018
Abstract: The purpose of the present study was to investigate muscle hypertrophy, strength, and myonuclear and satellite cell (SC) responses to high-frequency blood flow-restricted resistance exercise (BFRRE). Thirteen in iduals [24 ± 2 yr (mean ± SD), 9 men] completed two 5-day blocks of 7 BFRRE sessions, separated by a 10-day rest period. Four sets of unilateral knee extensions to voluntary failure at 20% of one repetition maximum (1RM) were conducted with partial blood flow restriction (90–100 mmHg). Muscle s les obtained before, during, 3 days, and 10 days after training were analyzed for muscle fiber area (MFA), myonuclei, SC, and mRNA and miRNA expression. Muscle size was measured by ultrasonography and magnetic resonance imaging and strength with 1RM knee extension. With the first block of BFRRE, SC number increased in both fiber types (70%–80%, P 0.05), whereas type I and II MFA decreased by 6 ± 7% and 15 ± 11% ( P 0.05), respectively. With the second block of training, muscle size increased by 6%–8%, whereas the number of SCs (type I: 80 ± 63%, type II: 147 ± 95%), myonuclei (type I: 30 ± 24%, type II: 31 ± 28%), and MFA (type I: 19 ± 19%, type II: 11 ± 19%) peaked 10 days after the second block of BFRRE, whereas strength peaked after 20 days of detraining (6 ± 6%, P 0.05). Pax7- and p21 mRNA expression were elevated during the intervention, whereas myostatin, IGF1R, MyoD, myogenin, cyclinD1 and -D2 mRNA did not change until 3–10 days postintervention. High-frequency low-load BFRRE induced robust increases in SC, myonuclei, and muscle size but modest strength gains. Intriguingly, the responses were delayed and peaked 10–20 days after the training intervention, indicating overreaching. NEW & NOTEWORTHY In line with previous studies, we demonstrate that high-frequency low-load blood flow-restricted resistance exercise (HF-BFRRE) can elicit robust increases in satellite cell and myonuclei numbers, along with gains in muscle size and strength. However, our results also suggest that these processes can be delayed and that with very strenuous HF-BFRRE, there may even be transient muscle fiber atrophy, presumably because of accumulated stress responses. Our findings have implications for the prescription of BFR exercise.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2014
DOI: 10.1038/SREP06697
Abstract: We assessed whether omega-3 index (red blood cell concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) was associated with insulin sensitivity and other metabolic outcomes in 47 overweight men aged 46.5 ± 5.1 years. Participants were assessed twice, 16 weeks apart. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Linear associations were examined stratified analyses were carried out with participants separated according to the omega-3 index: lower tertiles (LOI n = 31) and highest tertile (HOI n = 16). Increasing omega-3 index was correlated with higher insulin sensitivity (r = 0.23 p = 0.025), higher disposition index (r = 0.20 p = 0.054) and lower CRP concentrations (r = −0.39 p 0.0001). Insulin sensitivity was 43% higher in HOI than in LOI men (Matsuda index 6.83 vs 4.78 p = 0.009). Similarly, HOI men had disposition index that was 70% higher (p = 0.013) and fasting insulin concentrations 25% lower (p = 0.038). HOI men displayed lower nocturnal systolic blood pressure (−6.0 mmHg p = 0.025) and greater systolic blood pressure dip (14.7 vs 10.8% p = 0.039). Men in the HOI group also had lower concentrations of CRP (41% lower p = 0.033) and free fatty acids (21% lower, p = 0.024). In conclusion, higher omega-3 index is associated with increased insulin sensitivity and a more favourable metabolic profile in middle-aged overweight men.
Publisher: Frontiers Media SA
Date: 26-04-2022
Start Date: 10-2008
End Date: 06-2012
Amount: $165,923.00
Funder: Australian Research Council
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