ORCID Profile
0000-0001-9194-2033
Current Organisation
Victoria University
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Epigenetics (incl. Genome Methylation and Epigenomics) | Preventive Medicine | Exercise Physiology | Genetics
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Medical and Health Sciences |
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.EXGER.2015.12.010
Abstract: Na(+), K(+)-ATPase (NKA) isoforms (α1,α2,α3,β1,β2,β3) are involved in the maintenance of membrane potential and hence are important regulators of cellular homeostasis. Given the age-related decline in skeletal muscle function, we investigated whether the natural physiological process of aging is associated with altered abundance of NKA isoforms (α1,α2,α3,β1,β2,β3) or of the commonly used control protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Importantly, measurements were made in both whole muscle or specific fiber types obtained from skeletal muscle biopsies. Seventeen healthy older (AGED, 69.4 ± 3.5 years, mean ± SD) and 14 younger (YOUNG, 25.5 ± 2.8 years) adults underwent a muscle biopsy for biochemical analyses. Comparing homogenates from AGED and YOUNG in iduals revealed higher β3 isoform (p<0.05) and lower GAPDH (p<0.05). Analysis of in idual fibers in muscle from YOUNG in iduals, showed greater α3 and β2 isoforms, and more GAPDH in Type II compared with Type I fibers (p<0.05). In the AGED, GAPDH was higher in Type II compared with Type I fibers (p 0.05). Compared with the same fiber type in YOUNG, α1 was greater (Type I) and α3 lower (Type II), while in both fiber types, β2 was lower, β3 greater and GAPDH lower, in muscle from AGED in iduals (all p<0.05). Overall, we demonstrate that (i) GAPDH is an inappropriate choice of protein for normalization in all skeletal muscle research and (ii) full understanding of the role of NKA isoforms in human skeletal muscle requires consideration of age and muscle fiber type.
Publisher: Public Library of Science (PLoS)
Date: 21-11-2017
Publisher: MDPI AG
Date: 14-05-2021
DOI: 10.3390/NU13051666
Abstract: Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized that a high fat diet (60%) administered to developing male C57BL/6J mice that had not reached skeletal maturity would over represent bone microarchitectural implications, and that skeletally mature mice would better represent adult-onset glucose intolerance and the pre-diabetes phenotype. Two groups of developing (8 week) and mature (12 week) male C57BL/6J mice were placed onto either a normal chow (NC) or high fat diet (HFD) for 10 weeks. Oral glucose tolerance tests were performed throughout the study period. Long bones were excised and analysed for ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry and gene rotein expression analyses. The HFD increased fasting blood glucose and significantly reduced glucose tolerance in both age groups by week 7 of the diets. The HFD reduced biomechanical strength, both cortical and trabecular indices in the developing mice, but only affected cortical outcomes in the mature mice. Similar results were reflected in the 2D histomorphometry. Tibial gene expression revealed decreased bone formation in the HFD mice of both age groups, i.e., decreased osteocalcin expression and increased sclerostin RNA expression. In the mature mice only, while the HFD led to a non-significant reduction in runt-related transcription factor 2 (Runx2) RNA expression, this decrease became significant at the protein level in the femora. Our mature HFD mouse model more accurately represents late-onset impaired glucose tolerance re-T2DM cases in humans and can be used to uncover potential insights into reduced bone formation as a mechanism of skeletal fragility in these patients.
Publisher: Wiley
Date: 28-01-2020
Abstract: The renin angiotensin system (RAS) regulates fluid balance, blood pressure and maintains vascular tone. The potent vasoconstrictor angiotensin II (Ang II) produced by angiotensin‐converting enzyme (ACE) comprises the classical RAS. The non‐classical RAS involves the conversion of Ang II via ACE2 into the vasodilator Ang (1‐7) to counterbalance the effects of Ang II. Furthermore, ACE2 converts AngA into another vasodilator named alamandine. The over activation of the classical RAS (increased vasoconstriction) and depletion of the non‐classical RAS (decreased vasodilation) results in vascular dysfunction. Vascular dysfunction is the leading cause of atherosclerosis and cardiovascular disease (CVD). Additionally, local RAS is expressed in various tissues and regulates cellular functions. RAS dysregulation is involved in other several diseases such as inflammation, renal dysfunction and even cancer growth. An approach in restoring vascular dysfunction and other pathological diseases is to either increase the activity of ACE2 or reduce the effect of the classical RAS by counterbalancing Ang II effects. The antitrypanosomal agent, diminazene aceturate (DIZE), is one approach in activating ACE2. DIZE has been shown to exert beneficial effects in CVD experimental models of hypertension, myocardial infarction, type 1 diabetes and atherosclerosis. Thus, this review focuses on DIZE and its effect in several tissues such as blood vessels, cardiac, renal, immune and cancer cells.
Publisher: The Endocrine Society
Date: 30-11-2021
Abstract: Osteoglycin (OGN) is a proteoglycan released from bone and muscle which has been associated with markers of metabolic health. However, it is not clear whether the levels of circulating OGN change throughout the adult lifespan or if they are associated with clinical metabolic markers or fitness. We aimed to identify the levels of circulating OGN across the lifespan and to further explore the relationship between OGN and aerobic capacity as well as OGN’s association with glucose and HOMA-IR. 107 in iduals (46 males and 61 females) aged 21-87 years were included in the study. Serum OGN levels, aerobic capacity (VO2peak), glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed. T-tests were used to compare participant characteristics between sexes. Regression analyses were performed to assess the relationship between OGN and age, and OGN and fitness and metabolic markers. OGN displayed a nonlinear, weak “U-shaped” relationship with age across both sexes. Men had higher levels of OGN than women across the lifespan (β = 0.23, P = .03). Age and sex explained 16% of the variance in OGN (adjusted R2 = 0.16 P & .001). Higher OGN was associated with higher VO2peak (β = 0.02, P = .001) however, those aged & showed a stronger positive relationship than those aged & . A higher OGN level was associated with a higher circulating glucose level (β = 0.17, P & .01). No association was observed between OGN and HOMA-IR. OGN was characterized by a U-shaped curve across the lifespan which was similar between sexes. Those with a higher aerobic capacity or higher glucose concentration had higher OGN levels. Our data suggest an association between OGN and aerobic fitness and glucose regulation. Future studies should focus on exploring the potential of OGN as a biomarker for chronic disease.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.JSAMS.2016.10.016
Abstract: Glucocorticoids (GC) are commonly used in the treatment of inflammatory conditions. Chronic GC administration has severe side effects that can decrease exercise capacity and, as a result performance. The side effects of acute (single dose) and short term (<7 days) GC administration are less severe, therefore the impact on exercise performance is unclear. Consequently, it is of interest to determine the influence of acute and short term GC administration on exercise capacity and performance and investigate the relationship with metabolism. Review article. Included in the review were studies with healthy volunteers that reported exercise capacity and performance outcomes following acute and short term GC ingestion. Additionally, the relationship of exercise, GC ingestion and metabolism was investigated. Acute GC treatment appears to have minimal effects on exercise performance at intensities between 60 and 90% of VO Acute GC administration has a minimal effect on exercise capacity and performance while short-term GC administration is likely to improve performance. Future studies should focus on the effects of GC on exercise performance and exercise metabolism during and post exercise to determine the effects on exercise capacity.
Publisher: BMJ
Date: 14-11-2018
Publisher: JMIR Publications Inc.
Date: 25-02-2022
DOI: 10.2196/35776
Abstract: The unprecedented changes and isolation measures to contain COVID-19 have had multiple psychological and social impacts, with implications for professional and personal functioning. Evidence-informed interventions that can be rapidly implemented under pandemic conditions to support mental health during such times are urgently needed. The aim of this study was to determine the acceptability and preliminary outcomes of a daily online mental health promotion program for tertiary education staff during the COVID-19 pandemic. The “Victoria University (VU) Elevenses” program was delivered as an uncontrolled intervention at Victoria University (VU) in the western metropolitan region of Melbourne, Australia. In April 2020, an email invitation was sent to all academic and professional staff inviting them to: (1) participate in the program and (2) opt-in to the research component. The “VU Elevenses” program provided 10-15–minute microinterventions comprising lifestyle and well-being strategies to promote mental health via an online meeting platform at 11 AM each weekday. A mixed methods approach was used to evaluate the program, combining structured questionnaires with semistructured interviews to investigate the experiences of staff who participated in the program. Between 16 and 90 participants provided weekly program feedback. A total of 106 university staff opted into the longitudinal research component and 10 staff participated in the interviews. Participants reported high levels of satisfaction with sessions and perceived benefits for mental health. Approximately one quarter of participants reported moderate to severe symptoms of depression, anxiety, and stress at baseline, with significant reductions in these symptoms in the first 7 weeks of the program, corresponding with easing in mandatory isolation (“lockdown”) restrictions. Symptoms of depression, anxiety, and stress all increased when lockdown measures were reintroduced, but not to the same levels as found during the initial lockdown period. Overall changes in depression and anxiety from baseline to the end of the program were explained by changes in COVID-19–related distress, whereas changes in self-compassion explained changes in stress. We show that it is feasible and acceptable to develop and deliver a program of brief interventions in a timely manner, using a simple and accessible online platform. Although participation in the program was initially associated with reduced symptoms of depression, anxiety, and stress, participants’ mental health worsened with the reintroduction of a “lockdown” period. However, as symptoms of depression, anxiety, and stress did not return to levels observed at the start of the VU Elevenses program, participation in the uncontrolled intervention may have offered a protective benefit against the impact of the second significant lockdown period.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 22-01-2016
Publisher: Wiley
Date: 12-02-2018
DOI: 10.1111/APHA.13039
Abstract: The aim of this study was to investigate the effects of 4 consecutive simulated night shifts on glucose homeostasis, mitochondrial function and central and peripheral rhythmicities compared with a simulated day shift schedule. Seventeen healthy adults (8M:9F) matched for sleep, physical activity and dietary/fat intake participated in this study (night shift work n = 9 day shift work n = 8). Glucose tolerance and insulin sensitivity before and after 4 nights of shift work were measured by an intravenous glucose tolerance test and a hyperinsulinaemic euglycaemic cl respectively. Muscles biopsies were obtained to determine insulin signalling and mitochondrial function. Central and peripheral rhythmicities were assessed by measuring salivary melatonin and expression of circadian genes from hair s les respectively. Fasting plasma glucose increased (4.4 ± 0.1 vs. 4.6 ± 0.1 mmol L Only 4 days of simulated night shift work in healthy adults is sufficient to reduce insulin sensitivity which would be expected to increase the risk of T2D.
Publisher: American Physiological Society
Date: 15-08-2015
DOI: 10.1152/AJPENDO.00605.2014
Abstract: —Reactive oxygen species (ROS) produced in skeletal muscle may play a role in potentiating the beneficial responses to exercise however, the effects of exercise-induced ROS on insulin action and protein signaling in humans has not been fully elucidated. Seven healthy, recreationally active participants volunteered for this double-blind, randomized, repeated-measures crossover study. Exercise was undertaken with infusion of saline (CON) or the antioxidant N-acetylcysteine (NAC) to attenuate ROS. Participants performed two 1-h cycling exercise sessions 7–14 days apart, 55 min at 65% V̇o 2peak plus 5 min at 85%V̇o 2peak , followed 3 h later by a 2-h hyperinsulinemic euglycemic cl (40 mIU·min −1 ·m 2 ) to determine insulin sensitivity. Four muscle biopsies were taken on each trial day, at baseline before NAC infusion (BASE), after exercise (EX), after 3-h recovery (REC), and post-insulin cl (PI). Exercise, ROS, and insulin action on protein phosphorylation were evaluated with immunoblotting. NAC tended to decrease postexercise markers of the ROS rotein carbonylation ratio by −13.5% ( P = 0.08) and increase the GSH/GSSG ratio twofold vs. CON ( P 0.05). Insulin sensitivity was reduced (−5.9%, P 0.05) by NAC compared with CON without decreased phosphorylation of Akt or AS160. Whereas p-mTOR was not significantly decreased by NAC after EX or REC, phosphorylation of the downstream protein synthesis target kinase p70S6K was blunted by 48% at PI with NAC compared with CON ( P 0.05). We conclude that NAC infusion attenuated muscle ROS and postexercise insulin sensitivity independent of Akt signaling. ROS also played a role in normal p70S6K phosphorylation in response to insulin stimulation in human skeletal muscle.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 07-2021
Publisher: Springer Science and Business Media LLC
Date: 24-07-2019
DOI: 10.1007/S00198-019-05087-3
Abstract: One year of calcium supplementation in older women led to modest reductions in total osteocalcin and undercarboxylated osteocalcin (ucOC), with no changes in muscle or fat mass, or glycated haemoglobin. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control. Total osteocalcin (TOC) is a marker of bone turnover, while its undercarboxylated form has beneficial effects on glucose metabolism in mice. This post hoc analysis of a randomised double-blind, placebo-controlled trial examined whether 1 year of calcium supplementation affected circulating TOC, undercarboxylated osteocalcin (ucOC) or glycated haemoglobin (HbA1c) in 1368 older community-dwelling women (mean age 75.2 ± 2.7 years). Women enrolled in the Calcium Intake Fracture Outcome Study trial (1998-2003) were supplemented with 1.2 g/d of elemental calcium (in the form of calcium carbonate) or placebo. Circulating TOC, ucOC and HbA1c was measured at 1 year (1999). After 1 year of calcium supplementation, TOC and ucOC levels were 17% and 22% lower compared with placebo (mean 22.7 ± 9.1 vs. 27.3 ± 10.9 μg/L and 11.1 ± 4.9 vs. 13.0 ± 5.7 μg/L, both P < 0.001). Carboxylated osteocalcin/ucOC was 6% lower after calcium supplementation (P < 0.05). Despite this, no differences in HbA1c were observed (calcium, 5.2 ± 0.6 vs. placebo, 5.3 ± 0.8% P = 0.08). Calcium supplementation did not affect BMI, whole body lean or fat mass. In exploratory analyses, total calcium (dietary and supplemental) was inversely related to TOC and ucOC, indicating calcium intake is an important dietary determinant of osteocalcin levels. One year of calcium supplementation in older women led to modest reductions in TOC and ucOC, with no changes in muscle or fat mass, or HbA1c. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control.
Publisher: SAGE Publications
Date: 2016
DOI: 10.4137/CMC.S38116
Abstract: Left ventricular diastolic dysfunction (LVDD) is one of the earliest signs for abnormal cardiac function in patients with type 2 diabetes (T2DM). It is important to explore the risk factors that will assist in identifying the severity of the LVDD in this population. We examined the influences of fitness and fatness on the level of left ventricular (LV) impairment in patients with T2DM. Twenty-five patients (age: 64.0 ± 2.5 years, body mass index [BMI] = 36.0 ± 1.5 kg/m 2 , mean ± standard error of measurement) with T2DM and preserved systolic function, but impaired diastolic function, mitral valve (MV) E/e′, participated in the study. LV function was assessed using a stress echocardiograph, aerobic power was assessed with a sign- and symptom-limited graded exercise test, and the fatness level was assessed using Dual-energy X-ray absorptiometry and BMI. Patients in the higher 50% of BMI had higher lateral and septal MV E/e′ (~34% and ~25%, respectively, both P 0.001), compared to those in the lower 50% of BMI, with no difference in LV ejection fraction (LVEF) ( P 0.05). In addition, a higher BMI correlated with a higher lateral ( r = 0.62, P 0.001) and septal ( r = 0.56, P 0.01) E/é. There was no such relationship for VO 2peak . BMI and VO 2peak were not correlated with LV systolic function (ejection fraction). In in iduals with T2DM and diastolic dysfunction, a higher BMI was associated with worsening diastolic function independent of their aerobic capacity. The data provide a simple and practical approach for clinicians to assist in the early identification and diagnostics of functional changes in the heart diastolic function in this population.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2009
Publisher: Wiley
Date: 02-2016
DOI: 10.14814/PHY2.12700
Publisher: JMIR Publications Inc.
Date: 03-06-2016
DOI: 10.2196/RESPROT.5119
Publisher: Elsevier BV
Date: 03-2021
Publisher: Impact Journals, LLC
Date: 03-01-2020
Publisher: Wiley
Date: 04-2017
DOI: 10.14814/PHY2.13219
Publisher: The Endocrine Society
Date: 18-09-0007
Publisher: The Endocrine Society
Date: 18-05-2021
Abstract: The osteoblast-derived polypeptide, osteocalcin (OC), has been associated with lower risk of type 2 diabetes and metabolic syndrome (MetS) in several epidemiological studies. Animal studies have indicated the undercarboxylated form of OC (ucOC) drives its association with metabolic outcomes. We compared associations of ucOC and carboxylated OC (cOC) with MetS and its components in older men. A cross-sectional analysis of 2575 men aged ≥70 years and older resident in Perth, Western Australia. ucOC was assayed using a hydroxyapatite-binding method, and cOC calculated by subtracting ucOC from total OC. Main outcome measures were MetS and its components. Both lower serum ucOC and cOC levels, and the proportion of cOC (%cOC) were associated with less favorable metabolic parameters (higher waist circumference, triglyceride, glucose, blood pressure, and lower high-density lipoprotein cholesterol), whereas inverse associations were found with %ucOC. Men in the lowest quintile of ucOC had higher risk of MetS compared to men in the highest quintile (Q1 ≤ 7.7 vs Q5 & 13.8 ng/mL OR = 2.4 95% CI, 1.8-3.2). Men in the lowest quintile of cOC had higher risk of MetS compared to those in the highest quintile (≤ 5.8 vs & 13.0 ng/mL OR = 2.4 95% CI, 1.8-3.2). Lower concentrations of serum ucOC or cOC were associated with less favorable metabolic parameters and a higher risk of MetS. In contrast, a lower proportion of ucOC was associated with better metabolic parameters and lower MetS risk. Further research is warranted to determine whether ucOC and cOC are suitable biomarkers for cardiometabolic risk in men.
Publisher: Oxford University Press (OUP)
Date: 23-03-2022
Abstract: Does 12 weeks of high-intensity interval training (HIIT) result in greater improvements in cardio-metabolic and reproductive outcomes compared to standard moderate-intensity continuous training (MICT) in women with polycystic ovary syndrome (PCOS)? HIIT offers greater improvements in aerobic capacity, insulin sensitivity and menstrual cyclicity, and larger reductions in hyperandrogenism compared to MICT. Exercise training is recognized to improve clinical outcomes in women with PCOS, but little is known about whether HIIT results in greater health outcomes compared to standard MICT. This was a two-armed randomized clinical trial enrolling a total of 29 overweight women with PCOS between May 2016 and November 2019. Women with PCOS aged 18–45 years were randomly assigned to 12 weeks of either MICT (60–75% peak heart rate, N = 14) or HIIT (& % peak heart rate, N = 15), each completed three times per week. The primary clinical outcomes were aerobic capacity (VO2peak) and insulin sensitivity (euglycaemic–hyperinsulinaemic cl ). Secondary outcomes included hormonal profiles, menstrual cyclicity and body composition. Both HIIT and MICT improved VO2peak (HIIT Δ 5.8 ± 2.6 ml/kg/min, P & 0.001 and MICT Δ 3.2 ± 2 ml/kg/min, P & 0.001), however, the HIIT group had a greater improvement in aerobic capacity compared to MICT (β = 2.73 ml/kg/min, P = 0.015). HIIT increased the insulin sensitivity index compared to baseline (Δ 2.3 ± 4.4 AU, P = 0.007) and MICT (β = 0.36 AU, P = 0.030), and caused higher increases in sex hormone-binding globulin compared to MICT (β = 0.25 nmol/l, P = 0.002). HIIT participants were 7.8 times more likely to report improved menstrual cyclicity than those in the MICT group (odds ratio 7.8, P = 0.04). This study has a small s le size and the findings of the effect of the exercise interventions are limited to overweight reproductive-aged women, who do not have any co-existing co-morbidities that require medication. Exercise, regardless of intensity, has clear health benefits for women with PCOS. HIIT appears to be a more beneficial strategy and should be considered for promoting health and reducing cardio-metabolic risk in overweight women with PCOS. This work was supported by a Project Support Grant from the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in PCOS. The authors have no conflicts of interest to disclose. ACTRN12615000242527. 19 February 2015. 27 May 2016.
Publisher: Frontiers Media SA
Date: 09-01-2017
Publisher: Springer Science and Business Media LLC
Date: 21-11-2012
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.IJCARD.2016.11.023
Abstract: Resistance training (RT) has been utilised to target muscle dysfunction associated with Chronic Heart Failure (CHF). However, there is limited meta-analysis evidence to support its use as a standalone therapy. This meta-analysis examined the effects of RT on muscle strength (one repetition maximum, 1RM and Peak Torque), aerobic capacity (VO We searched Medline, EMBASE, Cochrane and CINAHL for studies published up to July 2016, combining terms related to the population (eg, heart failure, CHF) with terms for the intervention (eg, resistance, strength training) and the outcomes (eg, QoL, VO Ten studies including 240 participants were included in our meta-analysis (aged 48-76years, Ejection Fraction 18-37%). Training duration ranged from 8 to 24weeks and intensity up to 80% of 1RM. RT increased 1RM (standardised change score=0.60 95% Confidence Interval: 0.43, 0.77) but not strength measured via peak torque at 60°/s RT as a single intervention can increase muscle strength, aerobic capacity and QoL in patients with CHF and may offer an alternative approach, particularly for those unable to participate in aerobic training. The effect of RT on muscle strength is mainly during slow controlled movements and not during rapid movements. Older adults and patients with advanced CHF are underrepresented in RT trials and future studies should seek to optimise their inclusion.
Publisher: American Physiological Society
Date: 11-2016
DOI: 10.1152/JAPPLPHYSIOL.00558.2016
Abstract: Physical training increases skeletal muscle Na + ,K + -ATPase content (NKA) and improves exercise performance, but the effects of inactivity per se on NKA content and isoform abundance in human muscle are unknown. We investigated the effects of 23-day unilateral lower limb suspension (ULLS) and subsequent 4-wk resistance training (RT) on muscle function and NKA in 6 healthy adults, measuring quadriceps muscle peak torque fatigue and venous [K + ] during intense one-legged cycling exercise and skeletal muscle NKA content ([ 3 H]ouabain binding) and NKA isoform abundances (immunoblotting) in muscle homogenates (α 1-3 , β 1–2 ) and in single fibers (α 1–3 , β 1 ). In the unloaded leg after ULLS, quadriceps peak torque and cycling time to fatigue declined by 22 and 23%, respectively, which were restored with RT. Whole muscle NKA content and homogenate NKA α 1–3 and β 1–2 isoform abundances were unchanged with ULLS or RT. However, in single muscle fibers, NKA α 3 in type I (−66%, P = 0.006) and β 1 in type II fibers (−40%, P = 0.016) decreased after ULLS, with other NKA isoforms unchanged. After RT, NKA α 1 (79%, P = 0.004) and β 1 (35%, P = 0.01) increased in type II fibers, while α 2 (76%, P = 0.028) and α 3 (142%, P = 0.004) increased in type I fibers compared with post-ULLS. Despite considerably impaired muscle function and earlier fatigue onset, muscle NKA content and homogenate α 1 and α 2 abundances were unchanged, thus being resilient to inactivity induced by ULLS. Nonetheless, fiber type-specific downregulation with inactivity and upregulation with RT of several NKA isoforms indicate complex regulation of muscle NKA expression in humans.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2019
DOI: 10.1007/S00223-019-00600-6
Abstract: Low circulating levels of undercarboxylated osteocalcin (ucOC) is associated with a higher risk of cardiovascular disease, yet whether ucOC has a direct effect on endothelium-dependent vasorelaxation, or in proximity to its postulated receptor, the class CG protein-coupled receptor (GPCR6A), in blood vessels remains unclear. Immunohistochemistry and proximity ligation assays were used to localize the presence of ucOC and GPRC6A and to determine the physical proximity (< 40 nm) in radial artery segments collected from patients undergoing coronary artery bypass surgery (n = 6) which exhibited calcification (determined by Von Kossa) and aorta from New Zealand white rabbits exhibiting atherosclerotic plaques. Endothelium-dependent vasorelaxation was assessed using cumulative doses of acetylcholine in vitro on abdominal aorta of rabbits fed a normal chow diet (n = 10) and a 4-week atherogenic diet (n = 9) pre-incubated with ucOC (10 ng/mL) or vehicle. Both ucOC and GPRC6A were localized in human and rabbit diseased-blood vessels. Proximity ligation assay staining demonstrated physical proximity of ucOC with GPRC6A only within plaques in rabbit arteries and the endothelium layer of rabbit arterioles. Endothelium-dependent vasorelaxation was impaired in atherogenic abdominal aorta compared to healthy aorta and ucOC attenuated this impairment. ucOC attenuated impaired endothelium-dependent vasorelaxation in rabbit abdominal aorta following an atherogenic diet, however, this effect may be independent of GPRC6A. It is important that future studies determine the underlying cellular mechanisms by which ucOC effects blood vessels as well as whether it can be used as a therapeutic agent against the progression of atherosclerosis.
Publisher: Wiley
Date: 08-07-2022
DOI: 10.1002/JBMR.4631
Abstract: Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk however, its relationship with all‐cause and cause‐specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all‐cause and cause‐specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N‐propeptide (PINP), and collagen type 1 C‐terminal cross‐linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community‐dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer‐related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all‐cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06–1.18, p 0.001 PINP HR = 1.06, 95% CI 1.01–1.11, p = 0.009 CTX HR = 1.13, 95% CI 1.08–1.19, p 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow‐up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05–1.22, p = 0.001 CTX HR = 1.12, 95% CI 1.04–1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01–1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all‐cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all‐cause and cancer‐related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Publisher: Elsevier BV
Date: 06-2020
Publisher: JMIR Publications Inc.
Date: 06-04-2018
DOI: 10.2196/RESPROT.8865
Publisher: Springer Science and Business Media LLC
Date: 16-09-2016
DOI: 10.1007/S11657-016-0284-1
Abstract: Patients with type 2 diabetes mellitus have a higher risk of dental and/or orthopaedic implant failure. However, the mechanism behind this phenomenon is unclear, and animal studies may prove useful in shedding light on the processes involved. This review considers the available literature on rat models of diabetes and titanium implantation. The process of osseointegration whereby direct contact is achieved between bone and an implant surface depends on healthy bone metabolism. Collective evidence suggests that hyperglycaemia adversely affects bone turnover and the quality of the organic matrix resulting in an overall deterioration in the quality, resilience and structure of the bone tissue. This in turn results in compromised osseointegration in patients receiving dental and orthopaedic implants. The incidence of diabetes mellitus (DM), which is a chronic metabolic disorder resulting in hyperglycaemia, is rising. Of particular significance is the rising incidence of adult onset type 2 diabetes mellitus (T2DM) in an ageing population. Understanding the effects of hyperglycaemia on osseointegration will enable clinicians to manage health outcomes for patients receiving implants. Much of our understanding of how hyperglycaemia affects osseointegration comes from animal studies. In this review, we critically analyse the current animal studies. Our review has found that most studies used a type 1 diabetes mellitus (T1DM) rodent model and looked at a young male population of rodents. The pathophysiology of T1DM is however very different to that of T2DM and is not representative of T2DM, the incidence of which is rising in the ageing adult population. Genetically modified rats have been used to model T2DM, but none of these studies have included female rats and the metabolic changes in bone for some of these models used are not adequately characterized. Therefore, the review suggests that the study population needs to be broadened to include both T1DM and T2DM models, older rats as well as young rats, and importantly animals from both sexes to reflect more accurately clinical practice.
Publisher: MDPI AG
Date: 29-06-2018
DOI: 10.3390/NU10070847
Publisher: JMIR Publications Inc.
Date: 30-08-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2008
Publisher: SAGE Publications
Date: 2014
DOI: 10.4137/CMC.S14089
Abstract: This study will examine the effects of combined aerobic and resistance training on left ventricular remodeling in diabetic patients with diastolic dysfunction. This is the first randomized controlled trial to look for effects of combined strength training and aerobic exercise on myocardial function as well as other clinical, functional, or psychological parameters in diabetic patients with isolated diastolic dysfunction, and will provide important insights into the potential management strategies for heart failure with preserved ejection fraction. This is a prospective, randomized controlled investigator initiated single center trial. Diabetic patients with LV diastolic dysfunction suitable for exercise training intervention will be randomized to three months of a supervised combination of aerobic and strength training exercises, or supervised light stretching (control arm). Pre and post intervention assessment will include stress echocardiography, peak aerobic power with 12-lead ECG, dual-energy X-ray absorptiometry, muscle strength, the capacity to perform activities of daily living (ADLs), and questionnaires to assess self-perceived quality of life and symptoms of depression. The primary endpoint is to compare any change in tissue Doppler-derived LV systolic and early diastolic velocities. The current trial protocol has been approved by the Human Research Ethics Committee of Austin Health and the University of Melbourne, Melbourne. The study will be performed in accordance with the Declaration of Helsinki. The investigator, regardless of the outcome, will publish the results of the study. Australian New Zealand Clinical Trials Registry: ACTRN12610000943044.
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.IJCARD.2004.11.022
Abstract: Resistance training (RT) has been shown to improve chronic heart failure (CHF) patients' functional ability and quality of life. Despite these benefits RT has not always been recommend as a form of exercise principally because of a concern for acceleration of the left ventricular (LV) remodeling process. This study investigated the effects of 8 weeks RT on the LV structure and function of patients with CHF. Fifteen men who suffered from CHF were ided into either a RT program or non-training control group. Before and after 8 weeks of training patients underwent resting echocardiography to assess their end-diastolic and end-systolic dimensions (EDD and ESD, respectively), ejection fraction (EF), fractional shortening (FS) and stroke volume (SV). A repeated measured ANOVA showed that 8 weeks of RT had no significant effect on the LV measurements (group x time, p>0.05). Post training comparison, however, revealed that the EF and FS of the training group was significantly higher than in the control group (40.9+/-10.5% vs. 30.3+/-4.6%, p=0.029 and 25.0+/-7.0% vs. 17.4+/-3.1%, p=0.020 respectively). RT is a suitable method of training for CHF patients since it does not cause a reduction of LV contractility function or enhance myocardial deterioration as measured by EF and FS.
Publisher: Impact Journals, LLC
Date: 23-06-2020
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.BONE.2017.02.010
Abstract: There is a large in idual variation in the bone remodelling markers (BRMs) osteocalcin (OC), procollagen 1 N-terminal propeptide (P1NP) and β-isomerized C-terminal telopeptide (β-CTx), as well as undercarboxylated osteocalcin (ucOC), at rest and in response to exercise. α-actinin-3 (ACTN3), a sarcomeric protein, is expressed in skeletal muscle and osteoblasts and may influence BRM levels and the cross-talk between muscle and bone. We tested the levels of serum BRMs in α-actinin-3 deficient humans (ACTN3 XX) at baseline, and following a single bout of exercise. Forty-three healthy Caucasian in iduals were ided into three groups (ACTN3 XX, n=13 ACTN3 RX, n=16 ACTN3 RR, n=14). Participants completed a single session of High Intensity Interval Exercise (HIIE) on a cycle ergometer (8×2-min intervals at 85% of maximal power). Blood s les were taken before, immediately after, and three hours post exercise to identify the peak changes in serum BRMs. There was a stepwise increase in resting serum BRMs across the ACTN3 genotypes (XX>RX>RR) with significantly higher levels of tOC ~26%, P1NP ~34%, and β-CTX (~33%) in those with ACTN3 XX compared to ACTN3 RR. Following exercise BRMs and ucOC were higher in all three ACTN3 genotypes, with no significant differences between groups. Serum levels of tOC, P1NP and β-CTX are higher in men with ACTN3 XX genotype (α-actinin-3 deficiency) compared to RR and RX. It appears that the response of BRMs and ucOC to exercise is not explained by the ACTN3 genotype.
Publisher: Frontiers Media SA
Date: 16-09-2016
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: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JSBMB.2017.07.029
Abstract: Androgen deprivation therapy (ADT) decreases muscle mass and function but no human studies have investigated the underlying genetic or cellular effects. We tested the hypothesis that ADT will lead to changes in skeletal muscle gene expression, which may explain the adverse muscle phenotype seen clinically. We conducted a prospective cohort study of 9 men with localised prostate cancer who underwent a vastus lateralis biopsy before and after 4 weeks of ADT. Next-generation RNA sequencing was performed and genes differentially expressed following ADT underwent gene ontology mining using Ingenuity Pathway Analysis. Differential expression of genes of interest was confirmed by quantitative PCR (Q-PCR) on gastrocnemius muscle of orchidectomised mice and sham controls (n=11/group). We found that in men, circulating total testosterone decreased from 16.5±4.3nmol/L at baseline to 0.4±0.15nmol/L post-ADT (p<0.001). RNA sequencing identified 19 differentially expressed genes post-ADT (all p<0.05 after adjusting for multiple testing). Gene ontology mining identified 8 genes to be of particular interest due to known roles in androgen-mediated signalling ABCG1, ACTC1, ANKRD1, DMPK, THY1, DCLK1, CST3 were upregulated and SLC38A3 was downregulated post-ADT. Q-PCR in mouse gastrocnemius muscle confirmed that only one gene, Actc1 was concordantly upregulated (p<0.01) in orchidectomised mice compared with controls. In conclusion, given that ACTC1 upregulation is associated with improved muscle function in certain myopathies, we hypothesise that upregulation of ACTC1 may represent a compensatory response to ADT-induced muscle loss. Further studies will be required to evaluate the role and function of ACTC1.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.BONE.2019.03.015
Abstract: Osteocalcin (OC) is used as a surrogate marker for bone turnover in clinical settings. As bone mineral density (BMD) is largely heritable, we tested the hypothesis that a) bone-associated genetic variants previously identified in Genome-Wide Association Studies (GWAS) and combined into a genetic risk score (GRS) are associated with a) circulating levels of OC and b) the changes in OC following acute exercise. Total OC (tOC), undercarboxylated OC (ucOC), and carboxylated OC (cOC) were measured in serum of 73 healthy Caucasian males at baseline and after a single bout of high-intensity interval exercise. In addition, genotyping was conducted targeting GWAS variants previously reported to be associated with BMD and then combined into a GRS. Potential associations between the GRS and tOC, ucOC and cOC were tested with linear regressions adjusted for age. At baseline none of the in idual SNPs associated with tOC, ucOC and cOC. However, when combined, a higher GRS was associated with higher tOC (β = 0.193 ng/mL p = 0.037 95% CI = 0.012, 0.361) and cOC (β = 0.188 ng/mL p = 0.04 95% CI = 0.004, 0.433). Following exercise, GRS was associated with ucOC levels, (β = 3.864 ng/mL p-value = 0.008 95% CI = 1.063, 6.664) but not with tOC or cOC. Screening for genetic variations may assist in identifying people at risk for abnormal circulating levels of OC at baseline/rest. Genetic variations in BMD predicted the ucOC response to acute exercise indicating that physiological functional response to exercise may be influenced by bone-related gene variants.
Publisher: Springer Science and Business Media LLC
Date: 31-03-2022
DOI: 10.1186/S13690-022-00854-X
Abstract: Osteoarthritis (OA) is a chronic, progressive condition that can be effectively managed via conservative treatments including exercise, weight management and education. Offering these treatments contemporaneously and digitally may increase adherence and engagement due to the flexibility and cost-effectiveness of digital program delivery. The objective of this review was to summarise the characteristics of current digital self-management interventions for in iduals with OA and synthesise adherence and attrition outcomes. Electronic databases were searched for randomised controlled trials utilising digital self-management interventions in in iduals with OA. Two reviewers independently screened the search results and extracted data relating to study characteristics, intervention characteristics, and adherence and dropout rates. Eleven studies were included in this review. Intervention length ranged from 6 weeks to 9 months. All interventions were designed for in iduals with OA and mostwere multi-component and were constructed around physical activity. The reporting of intervention adherence varied greatly between studies and limited the ability to form conclusions regarding the impact of intervention characteristics. However, of the seven studies that quantified adherence, six reported adherence 70%. Seven of the included studies reported attrition rates 20%, with contact and support from researchers not appearing to influence adherence or attrition. Holistic digital interventions designed for a targeted condition are a promising approach for promoting high adherence and reducing attrition. Future studies should explore how adherence of digital interventions compares to face-to-face interventions and determine potential influencers of adherence.
Publisher: Frontiers Media SA
Date: 28-05-2021
DOI: 10.3389/FPUBH.2021.655491
Abstract: Since the beginning of time people explored and developed new technologies to make their activities of daily living less labour intense, more efficient and, consequently, more sedentary. In addition, technological advances in medicine throughout history have led to a substantial increase in life expectancy. However, the combination of increased sedentary behaviour and increased life-expectancy resulted in a sharp increase in overweight and obesity related chronic conditions and illness. Although people may live longer, they are doing so with poorer physical function and a reduced quality of life. In this review we explore how technological advances have influenced people's sedentary behaviour and, through the lens of the affective-reflective theory (ART), we propose a means by which technology could be repurposed to encourage greater engagement in physical activity.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.JSAMS.2007.10.007
Abstract: The one-repetition maximum (1RM) test is considered the gold standard for assessing muscle strength in non-laboratory situations. Since most previous 1RM reliability studies have been conducted with experienced young participants, it is unclear if acceptable test-retest reliability exists for untrained middle-aged in iduals. This study examined the reliability of the 1RM strength test of untrained middle-aged in iduals. Fifty-three untrained males (n=25) and females (n=28) aged 51.2+/-0.9 years participated in the study. Participants undertook the first 1RM test (T1) 4-8 days after a familiarisation session with the same exercises. 1RM was assessed for seven different exercises. Four to eight days after T1, participants underwent another identical 1RM test (T2). Ten weeks later, 27 participants underwent a third test (T3). Intraclass correlation coefficients (ICC), typical error as a coefficient of variation (TEcv), retest correlation, repeated measures ANOVA, Bland-Altman plots, and estimation of 95% confidence limits were used to assess reliability. A high ICC (ICC>0.99) and high correlation (r>0.9) were found for all exercises. TEcv ranged from 2.2 to 10.1%. No significant change was found for six of the seven exercises between T1 and T2. Leg press was slightly higher at T2 compared to T1 (1.6+/-0.6%, p=0.02). No significant change was found between T2 and T3 for any exercise. 1RM is a reliable method of evaluating the maximal strength in untrained middle-aged in iduals. It appears that 1RM-testing protocols that include one familiarisation session and one testing session are sufficient for assessing maximal strength in this population.
Publisher: Cold Spring Harbor Laboratory
Date: 14-05-2021
DOI: 10.1101/2021.05.14.444149
Abstract: Loss of functional β-cell mass is a key factor contributing to the poor glycaemic control in type 2 diabetes. However, therapies that directly target these underlying processes remains lacking. Here we demonstrate that gene expression of neuropeptide Y1 receptor and its ligand, neuropeptide Y, was significantly upregulated in human islets from subjects with type 2 diabetes. Importantly, the reduced insulin secretion in type 2 diabetes was associated with increased neuropeptide Y and Y1 receptor expression in human islets. Consistently, pharmacological inhibition of Y1 receptors by BIBO3304 significantly protected β-cells from dysfunction and death under multiple diabetogenic conditions in islets. In a preclinical study, Y1 receptor antagonist BIBO3304 treatment improved β-cell function and preserved functional β-cell mass, thereby resulting in better glycaemic control in both high-fat-diet/multiple low-dose streptozotocin- and db/db type 2 diabetic mice. Collectively, our results uncovered a novel causal link of increased islet NPY-Y1 receptor signaling to β-cell dysfunction and failure in human type 2 diabetes. These results further demonstrate that inhibition of Y1 receptor by BIBO3304 represents a novel and effective β-cell protective therapy for improving functional β-cell mass and glycaemic control in type 2 diabetes.
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: Springer Science and Business Media LLC
Date: 02-12-2012
DOI: 10.1007/S11897-011-0078-0
Abstract: It is now accepted that exercise training is a safe and effective therapeutic intervention to improve clinical status, functional capacity, and quality of life in people with chronic heart failure (CHF). Nevertheless, this therapeutic modality remains underprescribed and underutilized. Both aerobic and resistance training improve exercise capacity and may partially reverse some of the cardiac, vascular, and skeletal muscle abnormalities in in iduals with CHF. Aerobic training has more beneficial effects on aerobic power (peak oxygen consumption) and cardiac structure and function than resistance exercise training, while the latter is more effective for increasing muscle strength and endurance and promoting favorable arterial remodeling. Combined aerobic and resistance training is the preferred exercise intervention to reverse or attenuate the loss of muscle mass and improve exercise and functional capacity, muscle strength, and quality of life in in iduals with CHF. The challenge now is to translate these research findings into clinical practice.
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: JMIR Publications Inc.
Date: 09-04-2021
DOI: 10.2196/18777
Abstract: Bone and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism. The proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality. A total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function. The trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019. This study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions. Australia New Zealand Clinical Trials Registry ACTRN12618001756213 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375925. DERR1-10.2196/18777
Publisher: MDPI AG
Date: 16-07-2020
DOI: 10.3390/NU12072108
Abstract: Hyperglycaemia has a toxic effect on blood vessels and promotes coronary artery disease. It is unclear whether the dysfunction caused by hyperglycaemia is blood vessel specific and whether the dysfunction is exacerbated following an atherogenic diet. Abdominal aorta, iliac, and mesenteric arteries were dissected from New Zealand White rabbits following either a 4-week normal or atherogenic diet (n = 6–12 per group). The arteries were incubated ex vivo in control or high glucose solution (20 mM or 40 mM) for 2 h. Isometric tension myography was used to determine endothelial-dependent vasodilation. The atherogenic diet reduced relaxation as measured by area under the curve (AUC) by 25% (p 0.05), 17% (p = 0.06) and 40% (p = 0.07) in the aorta, iliac, and mesenteric arteries, respectively. In the aorta from the atherogenic diet fed rabbits, the 20 mM glucose altered EC50 (p 0.05). Incubation of the iliac artery from atherogenic diet fed rabbits in 40 mM glucose altered EC50 (p 0.05). No dysfunction occurred in the mesentery with high glucose incubation following either the normal or atherogenic diet. High glucose induced endothelial dysfunction appears to be blood vessel specific and the aorta may be the optimal artery to study potential therapeutic treatments of hyperglycaemia induced endothelial dysfunction.
Publisher: SAGE Publications
Date: 2015
DOI: 10.4137/CMC.S26230
Abstract: High-intensity interval exercise (HIIE) has gained popularity in recent years for patients with cardiovascular and metabolic diseases. Despite potential benefits, concerns remain about the safety of the acute response (during and/or within 24 hours postexercise) to a single session of HIIE for these cohorts. Therefore, the aim of this study was to perform a systematic review to evaluate the safety of acute HIIE for people with cardiometabolic diseases. Electronic databases were searched for studies published prior to January 2015, which reported the acute responses of patients with cardiometabolic diseases to HIIE (≥80% peak power output or ≥85% peak aerobic power, VO 2peak ). Eleven studies met the inclusion criteria (n = 156 clinically stable, aged 27-66 years), with 13 adverse responses reported (~8% of in iduals). The rate of adverse responses is somewhat higher compared to the previously reported risk during moderate-intensity exercise. Caution must be taken when prescribing HIIE to patients with cardiometabolic disease. Patients who wish to perform HIIE should be clinically stable, have had recent exposure to at least regular moderate-intensity exercise, and have appropriate supervision and monitoring during and after the exercise session.
Publisher: Springer Science and Business Media LLC
Date: 08-03-2016
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: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2011
Publisher: Elsevier BV
Date: 2022
Publisher: Frontiers Media SA
Date: 06-12-2021
DOI: 10.3389/FENDO.2021.781763
Abstract: To investigate the serum, plasma and urine levels of lipocalin-2 (LCN2) variants in healthy humans and their associations with risk factors for cardiometabolic (CMD) and chronic kidney (CKD) diseases. Fifty-nine males and 41 females participated in the study. Blood and urine were collected following an overnight fasting. LCN2 variants were analyzed using validated in-house ELISA kits. Heart rate, blood pressure, lipids profile, glucose, adiponectin, high-sensitivity C-reactive protein (hsCRP), creatinine, cystatin C, and biomarkers for kidney function were assessed. The levels of hLcn2, C87A and R81E in serum and urine, but not plasma, were significantly higher in men than women. Increased levels of LCN2 variants, as well as their relative ratios, in serum and plasma were positively associated with body mass index, blood pressure, triglyceride and hsCRP ( P & .05). No significant correlations were found between these measures and hLcn2, C87A or R81E in urine. However, LCN2 variants in urine, but not plasma or serum, were correlated with biomarkers of kidney function ( P & .05). Both the serum and plasma levels of LCN2 variants, as well as their ratios are associated with increased cardiometabolic risk, whereas those in urine are correlated with renal dysfunction. LCN2 variants represent promising biomarkers for CMD and CKD.
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: Elsevier
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 13-03-2017
DOI: 10.1007/S00198-017-3994-3
Abstract: Undercarboxylated osteocalcin (ucOC) may play a role in glucose homeostasis and cardiometabolic health. This review examines the epidemiological and interventional evidence associating osteocalcin (OC) and ucOC with metabolic risk and cardiovascular disease. The complexity in assessing such correlations, due to the observational nature of human studies, is discussed. Several studies have reported that higher levels of ucOC and OC are correlated with lower fat mass and HbA1c. In addition, improved measures of glycaemic control via pharmacological and non-pharmacological (e.g. exercise or diet) interventions are often associated with increased circulating levels of OC and/or ucOC. There is also a relationship between lower circulating OC and ucOC and increased measures of vascular calcification and cardiovascular disease. However, not all studies have reported such relationship, some with contradictory findings. Equivocal findings may arise because of the observational nature of the studies and the inability to directly assess the relationship between OC and ucOC on glycaemic control and cardiovascular health in humans. Studying OC and ucOC in humans is further complicated due to numerous confounding factors such as sex differences, menopausal status, vitamin K status, physical activity level, body mass index, insulin sensitivity (normal/insulin resistance/T2DM), tissue-specific effects and renal function among others. Current observational and indirect interventional evidence appears to support a relationship between ucOC with metabolic and cardiovascular disease. There is also emerging evidence to suggest a direct role of ucOC in human metabolism. Further mechanistic studies are required to (a) clarify causality, (b) explore mechanisms involved and
Publisher: Springer Science and Business Media LLC
Date: 10-10-2019
DOI: 10.1007/S00198-018-4719-Y
Abstract: Bone remodeling markers (BRMs) are suppressed following the consumption of a meal. Our findings indicate that a single session of continuous moderate-intensity exercise, but not low-volume high-intensity interval exercise, performed 1 h after a meal attenuates the postprandial suppression of BRMs. Acute exercise transiently increases BRMs including osteocalcin (tOC) and the undercarboxylated form of osteocalcin (ucOC), a hormone that is implicated in glucose regulation. The effects of acute exercise and exercise-intensity on postprandial levels of tOC and ucOC are unknown. Twenty-seven adults that were overweight or obese (age 30 ± 1 years BMI 30 ± 1 kg∙m Compared to baseline, serum tOC and ucOC were suppressed 3 h after breakfast on the rest day (- 10 ± 1% and - 6 ± 2%, respectively p < 0.05), whereas ucOC/tOC was elevated (2.5 ± 1% p = 0.08). Compared to the rest day, CMIE attenuated the postprandial-induced suppression of tOC (rest day - 10 ± 2% versus CMIE - 5 ± 2%, p < 0.05) and ucOC (rest day - 6 ± 4% versus CMIE 11 ± 2%, p < 0.05), and increased postprandial ucOC/tOC (rest day 3 ± 2% versus CMIE 15 ± 1%, p 0.1). Acute CMIE, but not LV-HIIE, attenuates the postprandial-induced suppression of tOC and ucOC. CMIE may be an effective tool to control the circulating levels of BRMs following meal consumption in overweight/obese adults.
Publisher: American Physiological Society
Date: 11-2018
DOI: 10.1152/AJPREGU.00096.2018
Abstract: It remains unclear whether high-intensity interval exercise (HIIE) elicits distinct molecular responses to traditional endurance exercise relative to the total work performed. We aimed to investigate the influence of exercise intensity on acute perturbations to skeletal muscle mitochondrial function (respiration and reactive oxygen species) and metabolic and redox signaling responses. In a randomized, repeated measures crossover design, eight recreationally active in iduals (24 ± 5 yr V̇o 2peak : 48 ± 11 ml·kg −1 ·min −1 ) undertook continuous moderate-intensity [CMIE: 30 min, 50% peak power output (PPO)], high-intensity interval (HIIE: 5 × 4 min, 75% PPO, work matched to CMIE), and low-volume sprint interval (SIE: 4 × 30 s) exercise, ≥7 days apart. Each session included muscle biopsies at baseline, immediately, and 3 h postexercise for high-resolution mitochondrial respirometry ( Jo 2 ) and H 2 O 2 emission ( Jh 2 o 2 ) and gene and protein expression analysis. Immediately postexercise and irrespective of protocol, Jo 2 increased during complex I + II leak/state 4 respiration but Jh 2 o 2 decreased ( P 0.05). AMP-activated protein kinase and acetyl co-A carboxylase phosphorylation increased ~1.5 and 2.5-fold respectively, while thioredoxin-reductase-1 protein abundance was ~35% lower after CMIE vs. SIE ( P 0.05). At 3 h postexercise, regardless of protocol, Jo 2 was lower during both ADP-stimulated state 3 OXPHOS and uncoupled respiration ( P 0.05) but Jh 2 o 2 trended higher ( P 0.08) and PPARGC1A mRNA increased ~13-fold, and peroxiredoxin-1 protein decreased ~35%. In conclusion, intermittent exercise performed at high intensities has similar dynamic effects on muscle mitochondrial function compared with endurance exercise, irrespective of whether total workload is matched. This suggests exercise prescription can accommodate in idual preferences while generating comparable molecular signals known to promote beneficial metabolic adaptations.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.IJCARD.2007.11.046
Abstract: It is not clear if men and women with high numbers of risk factors (HiMF) for metabolic syndrome (MetS) have impaired capacities to perform activities of daily living (ADL's) and lower quality of life (QoL) in the absence of symptomatic heart disease. Our results indicate that in women there is a correlation between the number of risk factors and the capacity to perform ADL's and QoL. This was not evident for men. These findings may partly explain why women tend to consult healthcare practitioners earlier in the disease process than men.
Publisher: Copernicus GmbH
Date: 06-07-2017
Publisher: Wiley
Date: 03-12-2021
DOI: 10.1002/JBMR.4208
Abstract: Evidence from animal models suggests that undercarboxylated osteocalcin (ucOC) is involved in muscle mass maintenance and strength. In humans, the ucOC to total (t)OC ratio may be related to muscle strength and perhaps physical function and falls risk, but data are limited. We tested the hypothesis that ucOC and ucOC/tOC ratio are associated with muscle function (muscle strength and physical function) in older women and 15‐year falls‐related hospitalizations. Serum tOC and ucOC were assessed in 1261 older women (mean age 75.2 ± 2.7 years) forming the Perth Longitudinal Study of Aging Women (1998 to 2013). Timed‐up‐and‐go (TUG) and grip strength were assessed at baseline and at 5 years. Falls‐related hospitalizations (14.5‐year follow‐up) were captured by the Hospital Morbidity Data Collection, via the Western Australian Data Linkage System. At baseline, women with higher ucOC/tOC ratio (quartile 4) had slower TUG performance compared with quartile 1 (~0.68 seconds, p .01). Grip strength and 5‐year change of TUG and grip were not different ( p .05) between quartiles. Fear of falling limiting house, outdoor, and combined activities was significantly different across quartiles ( p .05). Higher ucOC/tOC was significantly associated with poorer TUG performance at baseline and 5‐year change in performance, increased walking aid use, and fear of falling (all p .05). Higher ucOC was related to lower grip strength at baseline ( p .05) but not 5‐year change in strength. Those with the highest ucOC/tOC had greater falls‐related hospitalizations (unadjusted log rank, p = .004) remaining significant after adjusting for key variables (hazard ratio [HR] = 1.31, 95% confidence interval [CI] 1.09–1.57, p = .004). We identified a large proportion of older women with high ucOC/tOC ratio who had reduced physical function, including its long‐term decline and increased risk of falls‐related hospitalizations. Early identification of women at higher risk can enable prevention and intervention strategies to occur, reducing risk for injurious falls. © 2020 American Society for Bone and Mineral Research (ASBMR)..
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.JSAMS.2010.01.004
Abstract: Chronic heart failure (CHF) is a complex syndrome characterised by progressive decline in left ventricular function, low exercise tolerance and raised mortality and morbidity. Regular exercise participation has been shown to be a safe and effective treatment modality in the majority of CHF patients, partially reversing some of the maladaptations evident in myocardial and skeletal muscle function, and resulting in improvements in physical fitness and quality of life, and perhaps reduced mortality. The volume and intensity of exercise that is recommended depends on the syndrome severity, however in most patients it should consist of a combination of low-to-moderate intensity aerobic (endurance) exercise on most days of the week and in idually prescribed low-to-moderate intensity resistance (strength) training at least twice per week. Additionally, all patients should be closely monitored prior to and during exercise for contraindications by an appropriately trained health professional. The purpose of this statement is to inform and guide exercise practitioners and health professionals in the safe and effective prescription and supervision of exercise for patients with CHF.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Wiley
Date: 17-10-2021
DOI: 10.1002/JBM4.10561
Abstract: Circulating osteo progenitor (COP) cells are a heterogeneous population of cells that circulate within the peripheral blood with characteristics of the bone marrow mesenchymal stem and progenitor pool. Little is known about the behavior of this cell population in humans. The aim of this study was to identify whether a relationship exists between COP cells (as a percentage of the peripheral blood monocytic cells) and musculoskeletal morphometry and to identify if COP have potential clinical utility as a biomarker for osteoporosis. We recruited 57 older adults (median age: 69 years IQR: 65, 75 years) living independently in the community and performed cross‐sectional analysis to identify associations between the percentage of COP cells and body composition parameters, and through receiver operating characteristic analysis, we evaluated their ability to act as a biomarker of osteoporosis. COP cells were moderately associated with whole‐body bone mineral density (BMD) ( r = 0.323, p = 0.014) and bone mineral content (BMC) ( r = 0.387, p = 0.003), neck of femur BMD ( r = 0.473, p 0.001), and BMC ( r = 0.461, p 0.001) as well as appendicular lean mass (ALM) ( p = 0.038) and male sex ( p = 0.044) in univariable analysis. In multivariable analysis controlling for age, gender, height, and weight, COP cells remained strongly associated with neck of femur BMD ( p = 0.001) and content ( p = 0.003). COP cells were also a good predictor of osteoporosis (dual‐energy X‐ray absorptiometry [DXA] T ‐score −2.5) at the neck of femur (cutoff: 0.4% sensitivity: 100% specificity 79%) and total body (cutoff: 0.35% sensitivity: 80% specificity: 81%). This study shows strong relationships between bone parameters and COP cell number and male sex. They also have potential as a biomarker of osteoporosis, which may provide a new tool for advanced detection and screening in clinical settings. Future larger evaluation studies should verify the cutoffs for biomarker use, and further explore the relationship between COP cells and muscle. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Publisher: MDPI AG
Date: 24-02-2022
DOI: 10.3390/JCM11051232
Abstract: Background: This exploratory observational case–control study investigated the rate of referral to cardiac rehabilitation (CR) among patients hospitalised with heart failure (HF) and identified factors associated with referral. Methods: Patients hospitalised with HF as identified by the Victorian Cardiac Outcomes Registry HF study were included. Factors found to be univariately associated with referral were selected for multivariate logistic regression. Results: Among 1281 patients (mean age: 76.9 years 32.8% HFrEF and 33.9% HfpEF), 125 (9.8%) were referred to CR. Patients referred were younger (73.6 (2.7, 81.5) vs. 80.2 (71.1, 86.5) p 0.001) and were more likely to be men (72%, p 0.001). Factors associated with referral included inpatient percutaneous coronary intervention (OR, 3.31 95% CI, 1.04–10.48 p = 0.04), an aetiology of ischaemic or rhythm-related cardiomyopathy, and anticoagulants prescribed on discharge. Factors that lowered the likelihood of referral included older age, female, receiving inpatient oxygen therapy, and the presence of chronic obstructive pulmonary disease (COPD) or anaemia. Conclusions: The rate of referral to CR following hospitalisation with HF is low. Shortfalls are particularly evident among females, older patients, and in those with COPD or anaemia. Future studies should focus on improving referral processes and translating proven strategies that increase referrals to CR into practice.
Publisher: Wiley
Date: 12-04-2011
DOI: 10.1111/J.1464-5491.2011.03229.X
Abstract: To examine the oxygen (O(2)) kinetics during early recovery from peak exercise in patients with Type 2 diabetes and to examine whether oxygen O(2) recovery is associated with fasting glucose and HbA(1c) in this population. Eighty-nine participants (52 men) aged 51.8 ± 7.1 years (mean ± SD) were ided into three groups: normal weight (BMI ≤ 25.0 kg/m(2)), overweight/obese without diabetes (BMI ≥ 26 kg/m(2)) and overweight/obese with Type 2 diabetes. Participants were assessed for their aerobic power (VO(2peak)) on a cycle ergometer, provided a fasting blood s le and underwent a series of anthropometric measurements. Early recovery period was measured for 60 s from cessation of exercise and expressed as percentage of VO(2peak) (higher percentage represents slower recovery). No significant differences were observed for age between the three study groups. Both the overweight/obese groups without diabetes and with Type 2 diabetes had higher BMI than the normal weight group, with no significant differences between overweight/obese participants without diabetes and those with diabetes. Participants with Type 2 diabetes had lower VO(2peak) than overweight/obese participants without diabetes and normal weight in iduals (19.6 ± 4.8, 22.6 ± 5.4 and 25.7 ± 5.3 ml kg(-1) min(-1), respectively, P < 0.004 for overall trends). Participants with Type 2 diabetes also had slower recovery in oxygen O(2) kinetics after exercise, compared with both normal weight and overweight/obese in iduals without diabetes (56.5 ± 7.7, 49.2 ± 7.2, 47.7 ± 7.4%, P < 0.004 for overall trends). Multiple regression analysis revealed that percentage of oxygen O(2) recovery was a stronger predictor than VO(2peak), BMI or age for fasting glucose and HbA(1c). Patients with Type 2 diabetes have lower VO(2peak) and prolonged oxygen O(2) recovery from peak exercise. However, only prolonged oxygen O(2) recovery was associated with fasting glucose and HbA(1c).
Publisher: MDPI AG
Date: 04-10-2018
DOI: 10.3390/NU10101426
Abstract: There is increasing evidence for the involvement of the skeleton in the regulation of atherosclerotic vascular disease. Osteocalcin, an osteoblast derived protein, exists in two forms, carboxylated and undercarboxylated osteocalcin. Undercarboxylated osteocalcin has been linked to the regulation of metabolic functions, including glucose and lipid metabolism. Features of atherosclerosis have been associated with circulating osteocalcin however, this association is often conflicting and unclear. Therefore, the aim of this review is to examine the evidence for a role of osteocalcin in atherosclerosis development and progression, and in particular endothelial dysfunction and vascular calcification. The current literature suggests that undercarboxylated osteocalcin stimulates the phosphoinositide 3-kinase rotein kinase B (PI3K/Akt) signaling pathway to upregulate nitric oxide and nuclear factor kappa β (NF-кβ) in vascular cells, possibly protecting endothelial function and preventing atherogenesis. However, this effect may be mediated by metabolic factors, such as improvements in insulin signaling, rather than through a direct effect on the vasculature. Total osteocalcin is frequently associated with vascular calcification, an association that may occur as a result of vascular cells eliciting an osteogenic phenotype. Whether osteocalcin acts as a mediator or a marker of vascular calcification is currently unclear. As such, further studies that examine each form of osteocalcin are required to elucidate if it is a mediator of atherogenesis, and whether it functions independently of metabolic factors.
Publisher: Wiley
Date: 28-11-2019
DOI: 10.1002/CRE2.255
Publisher: Frontiers Media SA
Date: 05-05-2017
Publisher: Public Library of Science (PLoS)
Date: 09-02-2017
Publisher: SAGE Publications
Date: 2017
Abstract: Coronary artery disease (CAD) is a leading cause of disease burden worldwide. Referral to cardiac rehabilitation (CR) is a class I recommendation for all patients with CAD based on findings that participation can reduce cardiovascular and all-cause mortality, as well as improve functional capacity and quality of life. However, programme uptake remains low, systematic progression through the traditional CR phases is often lacking, and communication between health care providers is frequently suboptimal, resulting in fragmented care. Only 30% to 50% of eligible patients are typically referred to outpatient CR and fewer still complete the programme. In contemporary models of CR, patients are no longer treated by a single practitioner, but rather by an array of health professionals, across multiples specialities and health care settings. The risk of fragmented care in CR may be great, and a concerted approach is required to achieve continuity and optimise patient outcomes. ‘Continuity of care’ has been described as the delivery of services in a coherent, logical, and timely fashion and which entails 3 specific domains: informational, management, and relational continuity. This is examined in the context of CR.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.IJCARD.2004.05.061
Abstract: Resistance training increases the skeletal muscle strength and functional ability of chronic heart failure patients. However, there is limited data regarding the effect of resistance training on the hemodynamic responses and peak oxygen consumption (peak VO(2)) of chronic heart failure patients treated with beta-blocker. This study examined the effect of resistance training on hemodynamics, peak aerobic capacity, muscle strength and quality of life of chronic heart failure patients on beta-blockers medication. Fifteen men diagnosed with chronic heart failure were matched to either a resistance training program or non-training control group. At baseline and after 8 weeks of resistance training patients performed both Balke incremental and maximal strength tests and completed quality of life questionnaires. The resistance training group demonstrated a significant increase of walking time and peak VO(2) by 11.7% (p=0.002) and approximately 19% (p<0.05), respectively. Peak VO(2) was significantly correlated with both walking time (r=0.54, p=0.038) and change in total weight lifted (r=0.55, p=0.034). Quality of life significantly increased by 87% (p=0.030). The improvement in quality of life was correlated with post training peak VO(2) (r=0.58, p=0.025) and total weight lifted during the post maximal strength test (r=-0.52, p=0.047). The benefits from resistance training for chronic heart failure patients on beta-blocker medication included an increased aerobic and exercise capacity, skeletal muscle strength and most importantly, an improvement in the quality of life, which is the main goal of cardiac rehabilitation programs. Furthermore, with appropriate supervision, it is recommended that resistance exercise be added to the exercise rehabilitation program of these patients when possible.
Publisher: SAGE Publications
Date: 2017
Abstract: Psychological distress and depression are risk factors for cardiovascular disease (CVD). As such, a reduction in psychological distress and increase in positive well-being may be important to reduce the risk for future development of CVD. Exercise training may be a good strategy to prevent and assist in the management of psychological disorders. The psychological effects of the initial exercise sessions may be important to increase exercise adherence. The aims of this systematic review were (a) to examine whether acute aerobic, resistance, or a combination of the 2 exercises improves psychological well-being and reduces psychological distress in in iduals with healthy weight and those who are overweight/obese but free from psychological disorders, and (b) if so, to examine which form of exercise might yield superior results. The online database PubMed was searched for articles using the PICO (patient, intervention, comparison, and outcome) framework for finding scientific journals based on key terms. Forty-two exercise studies met the inclusion criteria. A total of 2187 participants were included (age: 18-64 years, body mass index [BMI]: 21-39 kg/m 2 ). Only 6 studies included participants with a BMI in the overweight/obese classification. Thirty-seven studies included aerobic exercise, 2 included resistance exercise, 1 used a combination of aerobic and resistance, and 2 compared the effects of acute aerobic exercise versus the effects of acute resistance exercise. The main findings of the review were that acute aerobic exercise improves positive well-being and have the potential to reduce psychological distress and could help reduce the risks of future CVD. However, due to the limited number of studies, it is still unclear which form of exercise yields superior psychological benefits. Obese, overweight, and healthy weight in iduals can exhibit psychological benefits from exercise in a single acute exercise session, and these positive benefits of exercise should be used by health professionals as a tool to increase long-term participation in exercise in these populations.
Publisher: Wiley
Date: 02-2015
DOI: 10.14814/PHY2.12294
Publisher: Public Library of Science (PLoS)
Date: 25-11-2020
DOI: 10.1371/JOURNAL.PONE.0242774
Abstract: There are conflicting reports on the association of undercarboxylated osteocalcin (ucOC) in cardiovascular disease development, including endothelial function and hypertension. We tested whether ucOC is related to blood pressure and endothelial function in older adults, and if ucOC directly affects endothelial-mediated vasodilation in the carotid artery of rabbits. In older adults, ucOC, blood pressure, pulse wave velocity (PWV) and brachial artery flow-mediated dilation (BAFMD) were measured (n = 38, 26 post-menopausal women and 12 men, mean age 73 ± 0.96). The vasoactivity of the carotid artery was assessed in male New Zealand White rabbits following a four-week normal or atherogenic diet using perfusion myography. An ucOC dose response curve (0.3–45 ng/ml) was generated following incubation of the arteries for 2-hours in either normal or high glucose conditions. ucOC levels were higher in normotensive older adults compared to those with stage 2 hypertension (p 0.05), particularly in women (p 0.01). In all participants, higher ucOC was associated with lower PWV (p 0.05), but not BAFMD (p 0.05). In rabbits, ucOC at any dose did not alter vasoactivity of the carotid artery, either following a normal or an atherogenic diet (p 0.05). Increased ucOC is associated with lower blood pressure and increased arterial stiffness, particularly in post-menopausal women. However, ucOC administration has no direct short-term effect on endothelial function in rabbit arteries. Future studies should explore whether treatment with ucOC, in vivo , has direct or indirect effects on blood vessel function.
Publisher: American Physiological Society
Date: 05-2020
DOI: 10.1152/JAPPLPHYSIOL.00850.2019
Abstract: This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure with reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration. Although daily supplementation increased plasma nitrite, our data indicate that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.JSAMS.2017.06.017
Abstract: Redox homeostasis and redox-sensitive protein signaling play a role in exercise-induced adaptation. The effects of sprint-interval exercise (SIE), high-intensity interval exercise (HIIE) and continuous moderate-intensity exercise (CMIE), on post-exercise plasma redox status are unclear. Furthermore, whether post-exercise plasma redox status reflects skeletal muscle redox-sensitive protein signaling is unknown. In a randomized crossover design, eight healthy adults performed a cycling session of HIIE (5×4min at 75% W Plasma hydrogen peroxide (H Plasma catalase activity was greater with SIE (56.6±3.8Uml Low-volume SIE elicited greater post-exercise plasma catalase activity compared to HIIE and CMIE, and greater H
Publisher: Elsevier BV
Date: 11-2017
Publisher: SAGE Publications
Date: 2015
DOI: 10.4137/CMC.S21372
Abstract: Reduced exercise tolerance is an independent predictor of hospital readmission and mortality in patients with heart failure (HF). Exercise training for HF patients is well established as an adjunct therapy, and there is sufficient evidence to support the favorable role of exercise training programs for HF patients over and above the optimal medical therapy. Some of the documented benefits include improved functional capacity, quality of life (QoL), fatigue, and dyspnea. Major trials to assess exercise training in HF have, however, focused on heart failure with reduced ejection fraction (HFREF). At least half of the patients presenting with HF have heart failure with preserved ejection fraction (HFPEF) and experience similar symptoms of exercise intolerance, dyspnea, and early fatigue, and similar mortality risk and rehospitalization rates. The role of exercise training in the management of HFPEF remains less clear. This article provides a brief overview of pathophysiology of reduced exercise tolerance in HFREF and heart failure with preserved ejection fraction (HFPEF), and summarizes the evidence and mechanisms by which exercise training can improve symptoms and HF. Clinical and practical aspects of exercise training prescription are also discussed.
Publisher: Informa UK Limited
Date: 23-08-2021
DOI: 10.1080/13697137.2021.1965118
Abstract: Osteoporosis and sarcopenia are two conditions associated with aging and characterized by a simultaneous decline in bone and muscle mass, respectively. These conditions share common risk factors (genetic, endocrine, nutritional and lifestyle factors) and biological pathways that often co-exist in a syndrome known as osteosarcopenia. Among the endocrine causes, estrogens play a critical role, especially in women. Estrogens have been demonstrated to exert a positive effect on bone and muscle development and maintenance. For this reason, menopause is characterized by a loss in bone mineral density and skeletal muscle quality and quantity. To date, studies indicate a positive effect of hormonal therapy on the prevention and management of osteoporosis, to the point that estrogen is prescribed as a first-line treatment for osteoporosis by the major international authorities. While results on sarcopenia are still disputable, such that estrogens are not recommended to prevent muscle loss in postmenopausal women, increased response to anabolic stimuli with estrogen therapy suggests similar beneficial effects on muscle as seen with bone, particularly when combined with resistance exercise.
Publisher: Springer Science and Business Media LLC
Date: 16-04-2019
Publisher: Bioscientifica
Date: 02-2019
DOI: 10.1530/EC-18-0473
Abstract: The aim of this study was to investigate the effect of a single dose of prednisolone on (A) high-intensity interval cycling performance and (B) post-exercise metabolic, hormonal and haematological responses. Nine young men participated in this double-blind, randomised, cross-over study. The participants completed exercise sessions (4 × 4 min cycling bouts at 90–95% of peak heart rate), 12 h after ingesting prednisolone (20 mg) or placebo. Work load was adjusted to maintain the same relative heart rate between the sessions. Exercise performance was measured as total work performed. Blood s les were taken at rest, immediately post exercise and up to 3 h post exercise. Prednisolone ingestion decreased total work performed by 5% ( P 0.05). Baseline blood glucose was elevated following prednisolone compared to placebo ( P 0.001). Three hours post exercise, blood glucose in the prednisolone trial was reduced to a level equivalent to the baseline concentration in the placebo trial ( P 0.05). Prednisolone suppressed the increase in blood lactate immediately post exercise ( P 0.05). Total white blood cell count was elevated at all time-points with prednisolone ( P 0.01). Androgens and sex hormone-binding globulin were elevated immediately after exercise, irrespective of prednisolone or placebo. In contrast, prednisolone significantly reduced the ratio of testosterone/luteinizing hormone ( P 0.01). Acute prednisolone treatment impairs high-intensity interval cycling performance and alters metabolic and haematological parameters in healthy young men. Exercise may be an effective tool to minimise the effect of prednisolone on blood glucose levels.
Publisher: Wiley
Date: 05-07-2016
DOI: 10.1002/JBMR.2884
Abstract: Undercarboxylated osteocalcin (ucOC) has been implicated in skeletal muscle insulin sensitivity and function. However, whether muscle mass and strength loss in atrophic conditions is related to a reduction in ucOC is not clear. We hypothesized that both immobilization and testosterone depletion would lead to reductions in ucOC, associated with not only the degree of muscle atrophy but also changes to atrophy signaling pathway(s) in male rats. We subjected 8-week-old male Fischer (F344) rats to 7 days of hindlimb immobilization 10 days after castration surgery. Hindlimb immobilization, but not castration, resulted in a significant reduction in ucOC (30%) and lower ucOC was correlated with the degree of muscle loss and muscle weakness. ucOC levels, the expression of ucOC-sensitive receptor G protein-coupled receptor, class C, group 6, member A (GPRC6A), as well as the activity of extracellular signal-regulated kinase (ERK) and 5' adenosine monophosphate-activated protein kinase (AMPK) were associated with the expression and activity of a number of proteins in the mammalian target of rapamycin complex 1 (mTORC1) and Forkhead Box O (FOXO) signaling pathways in a muscle type-specific manner. These data suggest that ucOC may have other effects on skeletal muscle in addition to its insulin sensitizing effect. © 2016 American Society for Bone and Mineral Research.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2011
DOI: 10.1007/S00198-010-1370-7
Abstract: The purpose of this study was to examine if the reduction in glucose post-exercise is mediated by undercarboxylated osteocalcin (unOC). Obese men were randomly assigned to do aerobic or power exercises. The change in unOC levels was correlated with the change in glucose levels post-exercise. The reduction in glucose post-acute exercise may be partly related to increased unOC. Osteocalcin (OC) in its undercarboxylated (unOC) form may contribute to the regulation of glucose homeostasis. As exercise reduces serum glucose and improves insulin sensitivity in obese in iduals and in iduals with type 2 diabetes (T2DM), we hypothesised that this benefit was partly mediated by unOC. Twenty-eight middle-aged (52.4 ± 1.2 years, mean ± SEM), obese (BMI = 32.1 ± 0.9 kg m(-2)) men were randomly assigned to do either 45 min of aerobic (cycling at 75% of VO(2peak)) or power (leg press at 75% of one repetition maximum plus jumping sequence) exercises. Blood s les were taken at baseline and up to 2 h post-exercise. At baseline, unOC was negatively correlated with glucose levels (r = -0.53, p = 0.003) and glycosylated haemoglobin (HbA1c) (r = -0.37, p = 0.035). Both aerobic and power exercises reduced serum glucose (from 7.4 ± 1.2 to 5.1 ± 0.5 mmol L(-1), p = 0.01 and 8.5 ± 1.2 to 6.0 ± 0.6 mmol L(-1), p = 0.01, respectively). Aerobic exercise significantly increased OC, unOC and high-molecular-weight adiponectin, while power exercise had a limited effect on OC and unOC. Overall, those with higher baseline glucose and HbA1c had greater reductions in glucose levels after exercise (r = -0.46, p = 0.013 and r = -0.43, p = 0.019, respectively). In a sub-group of obese people with T2DM, the percentage change in unOC levels was correlated with the percentage change in glucose levels post-exercise (r = -0.51, p = 0.038). This study reports that the reduction in serum glucose post-acute exercise (especially aerobic exercise) may be partly related to increased unOC.
Publisher: Wiley
Date: 12-06-2019
DOI: 10.1002/JBMR.3731
Abstract: Short-term administration of glucocorticoids (GCs) impairs muscle insulin sensitivity at least in part via the reduction of undercarboxylated osteocalcin (ucOC). However, whether ucOC treatment reverses the GC-induced muscle insulin resistance remains unclear. To test the hypothesis that ucOC directly ameliorates impaired insulin-stimulated glucose uptake (ISGU) induced by short-term GC administration in mice muscle and to identify the molecular mechanisms, mice were implanted with placebo or corticosterone (CS) slow-release pellets. Two days post-surgery, insulin-tolerance tests (ITTs) were performed. On day 3, serum was collected and extensor digitorum longus (EDL) and soleus muscles were isolated and treated ex vivo with vehicle, ucOC (30 ng/mL), insulin (60 µU/mL), or both. Circulating hormone levels, muscle glucose uptake, and muscle signaling proteins were assessed. CS administration reduced both serum osteocalcin and ucOC levels, whole-body insulin sensitivity, and muscle ISGU in EDL. Ex vivo ucOC treatment restored ISGU in CS-affected muscle, without increasing non-insulin-stimulated glucose uptake. In CS-affected EDL muscle, ucOC enhanced insulin action on phosphorylated (p-)protein kinase B (Akt)
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.JOCA.2015.12.008
Abstract: Using a mouse surgical model of post-traumatic osteoarthritis (OA), we sought to determine if muscle function is altered following acute joint injury and whether this relates to OA progression. Male C57BL/6 mice underwent surgical transection of the medio-meniscal tibial ligament destabilisation of the medial meniscus (DMM) or sham surgery on one knee. Tibialis anterior (TA) muscle function was assessed in situ at 1, 4 and 8 weeks post-surgery. Cartilage damage and joint inflammation were assessed by histologic scoring. Muscle mRNA expression was quantified by qRT-PCR. Tetanic and twitch force production between DMM and sham muscle did not differ at 1 week post-surgery. Muscle function improved in both groups with time, but specific force production in DMM muscles was 18% and 22% lower than sham muscles at 4 and 8 weeks post-surgery respectively. At 8 weeks post-surgery, DMM muscles had a 40% slower relaxation rate and reduced expression of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (Serca) pump mRNA compared to sham muscles both observations indicate likely alterations in muscle Ca(2+) handling. There were no histologic signs of muscle atrophy or inflammation in DMM TA muscles. Specific force production in both sham and DMM mice showed a negative correlation with the severity of joint inflammation. Acute knee injury in the DMM model of post-traumatic OA leads to a persistent deficit in TA muscle function that occurs in the absence of muscle atrophy. This study highlights that the impact of acute knee injury is unlikely to be limited to the muscles controlling knee movement.
Publisher: Wiley
Date: 03-2009
DOI: 10.1111/J.1464-5491.2009.02679.X
Abstract: Increases in inflammatory markers, hepatic enzymes and physical inactivity are associated with the development of the metabolic syndrome (MetS). We examined whether inflammatory markers and hepatic enzymes are correlated with traditional risk factors for MetS and studied the effects of resistance training (RT) on these emerging risk factors in in iduals with a high number of metabolic risk factors (HiMF, 2.9 +/- 0.8) and those with a low number of metabolic risk factors (LoMF, 0.5 +/- 0.5). Twenty-eight men and 27 women aged 50.8 +/- 6.5 years (mean +/- sd) participated in the study. Participants were randomized to four groups, HiMF training (HiMFT), HiMF control (HiMFC), LoMF training (LoMFT) and LoMF control (LoMFC). Before and after 10 weeks of RT [3 days/week, seven exercises, three sets with intensity gradually increased from 40-50% of one repetition maximum (1RM) to 75-85% of 1RM], blood s les were obtained for the measurement of pro-inflammatory cytokines, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT). At baseline, HiMF had higher interleukin-6 (33.9%), CRP (57.1%), GGT (45.2%) and ALT (40.6%) levels, compared with LoMF (all P < 0.05). CRP, GGT and ALT correlated with the number of risk factors (r = 0.48, 0.51 and 0.57, respectively, all P < 0.01) and with other anthropometric and clinical measures (r range from 0.26 to 0.60, P 0.05). HiMF was associated with increased inflammatory markers and hepatic enzyme concentrations. RT did not reduce inflammatory markers and hepatic enzymes in in iduals with HiMF.
Publisher: Wiley
Date: 17-09-2018
DOI: 10.1002/JBMR.3574
Abstract: In mice, glucocorticoid-induced insulin resistance occurs largely through impaired osteoblast function and decreased circulating undercarboxylated osteocalcin (ucOC). Whether these mechanisms contribute to glucocorticoid-induced insulin resistance in humans has yet to be established. In addition, the effects of glucocorticoids on the exercise-induced increase in circulating ucOC and insulin sensitivity are also unknown. We hypothesized that acute glucocorticoid treatment would lead to basal and postexercise insulin resistance in part through decreased circulating ucOC and ucOC-mediated skeletal muscle protein signaling. Nine healthy men completed two separate cycling sessions 12 hours after ingesting either glucocorticoid (20 mg prednisolone) or placebo (20 mg Avicel). The homeostatic model assessment was used to assess basal insulin sensitivity and a 2-hour euglycemic-hyperinsulinemic cl was commenced 3 hours after exercise to assess postexercise insulin sensitivity. Serum ucOC and skeletal muscle protein signaling were measured. Single-dose glucocorticoid ingestion increased fasting glucose (27%, p < 0.01) and insulin (83%, p < 0.01), and decreased basal insulin sensitivity (-47%, p < 0.01). Glucocorticoids reduced insulin sensitivity after cycling exercise (-34%, p < 0.01), reduced muscle GPRC6A protein content (16%, p < 0.05), and attenuated protein phosphorylation of mTOR
Publisher: Wiley
Date: 11-04-2023
DOI: 10.1113/JP283990
Abstract: Immobilization leads to muscle wasting and insulin resistance, particularly during ageing. It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti‐osteoporosis treatment, might protect muscle wasting independent of ucOC. We hypothesize that the combination of ucOC and ibandronate (IBN) treatments has superior protective effects against immobilization‐induced muscle wasting and insulin resistance than either treatment alone. C57BL/6J mice were hindlimb‐immobilized for two weeks, with injections of vehicle, ucOC (90 ng/g daily) and/or IBN (2 μg/g weekly). Insulin/oral glucose tolerance tests (ITT/OGTT) were performed. Immediately after immobilization, muscles (extensor digitorum longus (EDL), soleus, tibialis anterior, gastrocnemius and quadriceps) were isolated and measured for muscle mass. Insulin‐stimulated glucose uptake (EDL and soleus) was examined. Phosphorylation/expression of proteins in anabolic/catabolic pathways were examined in quadriceps. Primary human myotubes derived from older adult muscle biopsies were treated with ucOC and/or IBN, then signalling proteins were analysed. Combined treatment, but not in idual treatments, significantly increased the muscle weight/body weight ratio in immobilized soleus (31.7% P = 0.013) and quadriceps (20.0% P = 0.0008) muscles, concomitant with elevated p‐Akt (S473)/Akt ratio ( P = 0.0047). Combined treatment also enhanced whole‐body glucose tolerance (16.6% P = 0.0011). In human myotubes, combined treatment stimulated greater activation of ERK1/2 ( P = 0.0067 and 0.0072) and mTOR ( P = 0.036), and led to a lesser expression of Fbx32 ( P = 0.049) and MuRF1 ( P = 0.048) than in idual treatments. These findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing. image It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti‐osteoporosis treatment, might protect against muscle wasting independent of ucOC. The combination treatment of ucOC and ibandronate was shown to exert a greater therapeutic effect against immobilization‐induced muscle wasting, and led to greater activation of anabolic pathway and less expression of catabolic signalling proteins in myotubes derived from older adults, compared with in idual treatments. The combination treatment was found to improve whole‐body glucose tolerance. Our findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing.
Publisher: American Diabetes Association
Date: 09-2007
DOI: 10.2337/DC07-0841
Abstract: OBJECTIVE—There are limited data on the effects of resistance training on the capacity to perform activities of daily living (ADLs) and quality of life (QoL) for in iduals with a high number of metabolic risk factors (HiMF). In this study, we examined the effect of resistance training on the capacity to perform ADLs and QoL in in iduals with HiMF and compared any benefits with in iduals with a low number of metabolic risk factors (LoMF). RESEARCH DESIGN AND METHODS—Fifty-five untrained in iduals, aged 50.8 ± 6.5 years, were randomized to four groups: HiMF training (HiMFT), HiMF control, LoMF training (LoMFT), and LoMF control. At baseline and after 10 weeks of resistance training, participants underwent anthropometric measurements and assessments of aerobic power (Vo2peak), muscle strength, capacity to perform ADLs, and a self-perceived QoL questionnaire. A repeated-measures ANOVA was used to examine the effect of training over time among groups. RESULTS—Training increased lean body mass in both HiMFT (P = 0.03) and LoMFT (P = 0.03) groups. Total fat content and Vo2peak improved in the LoMFT group only. Muscle strength improved in both training groups (P & 0.01). Time to complete ADLs was reduced by 8.8% in the LoMFT group (P & 0.01) and 9.7% in the HiMF group (P & 0.01). Only the HiMFT group reported improvement in QoL. CONCLUSIONS— Resistance training improved muscle strength and the capacity to perform ADLs in in iduals with HiMF and LoMF. Resistance training improved QoL for the HiMF group, and this result was independent of changes in body fat content or aerobic power. Longer training regimens may be needed to improve QoL in in iduals with LoMF.
Publisher: Wiley
Date: 23-04-2017
DOI: 10.1113/JP273950
Publisher: Public Library of Science (PLoS)
Date: 25-11-2013
Publisher: MDPI AG
Date: 17-07-2020
DOI: 10.3390/NU12072132
Abstract: Heart failure with reduced ejection fraction (HFrEF) is a common end point for patients with coronary artery disease and it is characterized by exercise intolerance due, in part, to a reduction in cardiac output. Nitric oxide (NO) plays a vital role in cardiac function and patients with HFrEF have been identified as having reduced vascular NO. This pilot study aimed to investigate if nitrate supplementation could improve cardiac measures during acute, submaximal exercise. Five male participants (61 ± 3 years) with HFrEF (EF 32 ± 2.2%) completed this pilot study. All participants supplemented with inorganic nitrate (beetroot juice) or a nitrate-depleted placebo for ~13 days prior to testing. Participants completed a three-stage submaximal exercise protocol on a recumbent cycle ergometer with simultaneous echocardiography for calculation of cardiac output (Q), stroke volume (SV), and total peripheral resistance (TPR). Heart rate and blood pressure were measured at rest and during each stage. Both plasma nitrate (mean = ~1028%, p = 0.004) and nitrite (mean = ~109%, p = 0.01) increased following supplementation. There were no differences between interventions at rest, but the percent change in SV and Q from rest to stage two and stage three of exercise was higher following nitrate supplementation (all p 0.05, ES 0.8). Both interventions showed decreases in TPR during exercise, but the percent reduction TPR in stages two and three was greater following nitrate supplementation (p = 0.09, ES = 0.98 and p = 0.14, ES = 0.82, respectively). There were clinically relevant increases in cardiac function during exercise following supplementation with nitrate. The findings from this pilot study warrant further investigation in larger clinical trials.
Publisher: Wiley
Date: 15-04-2020
DOI: 10.1111/JGS.16428
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: Wiley
Date: 13-09-2022
DOI: 10.1002/JBM4.10667
Abstract: Osteoglycin (OGN) is a leucine‐rich proteoglycan that has been implicated in the regulation of glucose in animal models. However, its relationship with glucose control in humans is unclear. We examined the effect of high‐intensity interval exercise (HIIE) and hyperinsulinemic‐euglycemic cl on circulating levels of OGN as well as whether circulating OGN levels are associated with markers of glycemic control and cardio‐metabolic health. Serum was analyzed for OGN (ELISA) levels from 9 middle‐aged obese men (58.1 ± 2.2 years, body mass index [BMI] = 33.1 ± 1.4 kg∙m −2 , mean ± SEM) and 9 young men (27.8 ± 1.6 years, BMI = 24.4 ± 0.08 kg∙m −2 ) who previously completed a study involving a euglycemic‐hyperinsulinemic cl at rest and after HIIE (4x4 minutes cycling at approximately 95% peak heart rate (HRpeak), interspersed with 2 minutes of active recovery). Blood pressure, body composition (dual‐energy X‐ray absorptiometry), and insulin sensitivity (hyperinsulinemic‐euglycemic cl ) were assessed. Serum OGN was higher in the young cohort compared with the middle‐aged cohort (65.2 ± 10.1 ng/mL versus 36.5 ± 4. 5 ng/mL, p ≤ 0.05). Serum OGN was unaffected by acute HIIE but decreased after the insulin cl compared with baseline (~−27%, p = 0.01), post‐exercise (~−35%, p = 0.01), and pre‐cl (~−32%, p = 0.02) time points, irrespective of age. At baseline, lower circulating OGN levels were associated with increased age, BMI, and fat mass, whereas higher OGN levels were related to lower fasting glucose. Higher OGN levels were associated with a higher glucose infusion rate. Exercise had a limited effect on circulating OGN. The mechanisms by which OGN affects glucose regulation should be explored in the future. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.JSBMB.2017.01.022
Abstract: Muscle function is often impaired in patients with knee osteoarthritis (OA), with reduced strength and increased pain. The role of vitamin D and the vitamin D-endocrine pathway in muscle health has recently been placed in the spotlight, with various groups reporting positive effects on muscle development, function and health. Recently, it has been shown that uptake into muscle of the specialized vitamin D binding protein (DBP) is dependent on the endocytic receptor, megalin. Here we analyse circulating vitamin D, and muscle DBP, megalin and the cognate vitamin D receptor (VDR) in patients with knee OA and compare them to asymptomatic controls. Muscle and blood s les were collected from 19 patients with end-stage OA of the knee and 10 age-matched controls. Muscle biopsies from the OA group were performed during knee replacement surgery and a needle biopsy was used on control volunteers. Immunoblots performed with specific antibodies were used to detect the presence of DBP, megalin, VDR (using the specific D-6 antibody) and albumin in the muscle biopsies. Results were correlated with FoxO1, a key regulator of the ubiquitin-proteasome degradation pathway in muscle. There were no differences in circulating levels of 25 (OH) vitamin D3 between the groups, and no subjects were vitamin D deficient. We found increased VDR, DBP and albumin protein in the muscle from patients with OA compared to controls, with no change in muscle megalin expression. Furthermore, DBP levels in the muscle correlated with FoxO1, suggesting an association between muscle protein breakdown and the activation of the vitamin D-endocrine pathway in muscle surrounding an OA affected joint. We show, for the first time, that the factors involved in the vitamin D-endocrine-pathway are present at higher levels in muscles from OA patients compared to asymptomatic controls. This is despite no differences in circulating 25 (OH) vitamin D levels between the groups. These findings indicate the activation of vitamin D pathway in these muscles that may provide a beneficial compensatory stimulation of the repair process in muscles that are subject to inflammatory and proteolytic processes.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2015
DOI: 10.1007/S00198-015-3273-0
Abstract: We tested whether GPRC6A, the putative receptor of undercarboxylated osteocalcin (ucOC), is present in mouse muscle and whether ucOC increases insulin sensitivity following ex vivo muscle contraction. GPPRC6A is expressed in mouse muscle and in the mouse myotubes from a cell line. ucOC potentiated the effect of ex vivo contraction on insulin sensitivity. Acute exercise increases skeletal muscle insulin sensitivity. In humans, exercise increases circulating ucOC, a hormone that increases insulin sensitivity in rodents. We tested whether GPRC6A, the putative receptor of ucOC, is present in mouse muscle and whether recombinant ucOC increases insulin sensitivity in both C2C12 myotubes and whole mouse muscle following ex vivo muscle contraction. Glucose uptake was examined in C2C12 myotubes that express GPRC6A following treatment with insulin alone or with insulin and increasing ucOC concentrations (0.3, 3, 10 and 30 ng/ml). In addition, glucose uptake, phosphorylated (p-)AKT and p-AS160 were examined ex vivo in extensor digitorum longus (EDL) dissected from C57BL/6J wild-type mice, at rest, following insulin alone, after muscle contraction followed by insulin and after muscle contraction followed by recombinant ucOC then insulin exposure. We observed protein expression of the likely receptor for ucOC, GPRC6A, in whole muscle sections and differentiated mouse myotubes. We observed reduced GPRC6A expression following siRNA transfection. ucOC significantly increased insulin-stimulated glucose uptake dose-dependently up to 10 ng/ml, in differentiated mouse C2C12 myotubes. Insulin increased EDL glucose uptake (∼30 %, p < 0.05) and p-AKT and p-AKT/AKT compared with rest (all p < 0.05). Contraction prior to insulin increased muscle glucose uptake (∼25 %, p < 0.05), p-AKT, p-AKT/AKT, p-AS160 and p-AS160/AS160 compared with contraction alone (all p < 0.05). ucOC after contraction increased insulin-stimulated muscle glucose uptake (∼12 % p < 0.05) and p-AS160 (<0.05) more than contraction plus insulin alone but without effect on p-AKT. In the absence of insulin and/or of contraction, ucOC had no significant effect on muscle glucose uptake. GPRC6A, the likely receptor of osteocalcin (OC), is expressed in mouse muscle. ucOC treatment augments insulin-stimulated skeletal muscle glucose uptake in C2C12 myotubes and following ex vivo muscle contraction. ucOC may partly account for the insulin sensitizing effect of exercise.
Publisher: JMIR Publications Inc.
Date: 19-12-2021
Abstract: he unprecedented changes and isolation measures to contain COVID-19 have had multiple psychological and social impacts, with implications for professional and personal functioning. Evidence-informed interventions that can be rapidly implemented under pandemic conditions to support mental health during such times are urgently needed. he aim of this study was to determine the acceptability and preliminary outcomes of a daily online mental health promotion program for tertiary education staff during the COVID-19 pandemic. he “Victoria University (VU) Elevenses” program was delivered as an uncontrolled intervention at Victoria University (VU) in the western metropolitan region of Melbourne, Australia. In April 2020, an email invitation was sent to all academic and professional staff inviting them to: (1) participate in the program and (2) opt-in to the research component. The “VU Elevenses” program provided 10-15–minute microinterventions comprising lifestyle and well-being strategies to promote mental health via an online meeting platform at 11 AM each weekday. A mixed methods approach was used to evaluate the program, combining structured questionnaires with semistructured interviews to investigate the experiences of staff who participated in the program. etween 16 and 90 participants provided weekly program feedback. A total of 106 university staff opted into the longitudinal research component and 10 staff participated in the interviews. Participants reported high levels of satisfaction with sessions and perceived benefits for mental health. Approximately one quarter of participants reported moderate to severe symptoms of depression, anxiety, and stress at baseline, with significant reductions in these symptoms in the first 7 weeks of the program, corresponding with easing in mandatory isolation (“lockdown”) restrictions. Symptoms of depression, anxiety, and stress all increased when lockdown measures were reintroduced, but not to the same levels as found during the initial lockdown period. Overall changes in depression and anxiety from baseline to the end of the program were explained by changes in COVID-19–related distress, whereas changes in self-compassion explained changes in stress. e show that it is feasible and acceptable to develop and deliver a program of brief interventions in a timely manner, using a simple and accessible online platform. Although participation in the program was initially associated with reduced symptoms of depression, anxiety, and stress, participants’ mental health worsened with the reintroduction of a “lockdown” period. However, as symptoms of depression, anxiety, and stress did not return to levels observed at the start of the VU Elevenses program, participation in the uncontrolled intervention may have offered a protective benefit against the impact of the second significant lockdown period.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.JSAMS.2013.01.005
Abstract: Chronic kidney disease (CKD) is prevalent, affecting 13% of adult Australians and poses increased risk for cardiovascular morbidity and mortality. This position article provides evidence-based guidelines on the role of exercise training for CKD patients and provides recommendations for prescribing and delivering exercise training. Position stand. Synthesis of published work within the field of exercise training and chronic kidney disease. Exercise training likely to provide benefits to CKD patients, including improvements in cardio-respiratory fitness, quality of life, sympatho-adrenal activity, muscle strength and increased energy intake and possible reduction in inflammatory biomarkers. Existing studies generally report small s le sizes, brief training periods and relatively high attrition rates. Exercise training appears to be safe for CKD patients with no deaths directly related to exercise training in over 30,000 patient-hours, although strict medical exclusion criteria in previous studies resulted in 25% of patients being excluded potentially impacting the generalisability of the findings. Aerobic exercise at an intensity of >60% of maximum capacity is recommended to improve cardio-respiratory fitness. Few data are available on resistance training and it is unclear whether this form of training retards catabolic/inflammatory processes typical of CKD. However, it should be considered important due to its proven beneficial effects on bone density and muscle mass. Due to the high prevalence and incidence of co-morbidities in CKD patients, exercise training programs should be prescribed and delivered by in iduals with appropriate qualifications and experience to recognise and accommodate co-morbidities and associated complications.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2018
Publisher: JMIR Publications Inc.
Date: 18-03-2020
Abstract: one and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism. he proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality. total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function. he trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019. his study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions. ustralia New Zealand Clinical Trials Registry ACTRN12618001756213 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375925. ERR1-10.2196/18777
Publisher: JMIR Publications Inc.
Date: 30-08-2017
Abstract: hronic heart failure is characterized by an inability of the heart to pump enough blood to meet the demands of the body, resulting in the hallmark symptom of exercise intolerance. Chronic underperfusion of the peripheral tissues and impaired nitric oxide bioavailability have been implicated as contributors to the decrease in exercise capacity in these patients. nitric oxide bioavailability has been identified as an important mediator of exercise tolerance in healthy in iduals, but there are limited studies examining the effects in patients with chronic heart failure. he proposed trial is designed to determine the effects of chronic inorganic nitrate supplementation on exercise tolerance in both patients with heart failure preserved ejection fraction (HFpEF) and heart failure reduced ejection fraction (HFrEF) and to determine whether there are any differential responses between the 2 cohorts. A secondary objective is to provide mechanistic insights into the 2 heart failure groups’ exercise responses to the nitrate supplementation. atients with chronic heart failure (15=HFpEF and 15=HFrEF) aged 40 to 85 years will be recruited. Following an initial screen cardiopulmonary exercise test, participants will be randomly allocated in a double-blind fashion to consume either a nitrate-rich beetroot juice (16 mmol nitrate/day) or a nitrate-depleted placebo (for 5 days). Participants will continue daily dosing until the completion of the 4 testing visits (maximal cardiopulmonary exercise test, submaximal exercise test with echocardiography, vascular function assessment, and vastus lateralis muscle biopsy). There will then be a 2-week washout period after which the participants will cross over to the other treatment and complete the same 4 testing visits. his study is funded by National Heart Foundation of Australia and Victoria University. Enrolment has commenced and the data collection is expected to be completed in mid 2018. The initial results are expected to be submitted for publication by the end of 2018. f inorganic nitrate supplementation can improve exercise tolerance in patients with chronic heart failure, it has the potential to aid in further refining the treatment of patients in this population. ustralian New Zealand Clinical Trials Registry ACTRN12615000906550 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368912 (Archived by WebCite at xymLMiFK)
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.BONE.2019.115085
Abstract: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease. Blood was collected in the morning after an overnight fast from 236 adult men (18 to 92 years old) free of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analyzed for total osteocalcin (tOC) and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/tOC and cOC/tOC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis. The normal ranges for young men (≤30 years) were: tOC 17.9-56.8 ng/mL, ucOC 7.1-22.0 ng/mL, cOC 8.51-40.3 ng/mL (2.5th to 97.5th quantiles). Aging was associated with a "U" shaped pattern for tOC, cOC and ucOC levels. ucOC/tOC ratio was higher, while cOC/tOC ratio was lower in men of advanced age. Age explained ∼31%, while body mass index explained ∼4%, of the variance in the ratios. We have defined normal reference ranges for the OC forms in Australian men and demonstrated that the OC ratios may be better measures, than the absolute values, to identify the age-related changes on OC in men. These ratios may be incorporated into future research and clinical trials, and their associations with prediction of events, such as fracture or diabetes risk, should be determined.
Publisher: Portico
Date: 03-02-2016
Publisher: Elsevier BV
Date: 11-2023
Publisher: MDPI AG
Date: 13-10-2016
DOI: 10.3390/NU8100631
Publisher: Springer International Publishing
Date: 2019
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000511660
Abstract: b i Background: /i /b Evidence suggests that lower serum undercarboxylated osteocalcin (ucOC) may be negatively associated with cardiometabolic health. We investigated whether in iduals with a suppression of ucOC following an increase in dietary vitamin K1 exhibit a relative worsening of cardiometabolic risk factors. b i Materials and Methods: /i /b Men ( i n /i = 20) and women ( i n /i = 10) aged 62 ± 10 years participated in a randomized, controlled, crossover study. The primary analysis involved using data obtained from participants following a high vitamin K1 diet (HK 4-week intervention of increased leafy green vegetable intake). High and low responders were defined based on the median percent reduction (30%) in ucOC following the HK diet. Blood pressure (resting and 24 h), arterial stiffness, plasma glucose, lipid concentrations, and serum OC forms were assessed. b i Results: /i /b Following the HK diet, ucOC and ucOC/tOC were suppressed more ( i /i & #x3c 0.01) in high responders (41 and 29%) versus low responders (12 and 10%). The reduction in ucOC and ucOC/tOC was not associated with changes in blood pressure, arterial stiffness, plasma glucose, or lipid concentrations in the high responders ( i /i & #x3e 0.05). b i Discussion/Conclusion: /i /b Suppression of ucOC via consumption of leafy green vegetables has no negative effects on cardiometabolic health, perhaps, in part, because of cross-talk mechanisms.
Location: Israel
Start Date: 2016
End Date: 2016
Funder: Jack Brockhoff Foundation
View Funded ActivityStart Date: 2020
End Date: 12-2024
Amount: $444,000.00
Funder: Australian Research Council
View Funded Activity