ORCID Profile
0000-0001-9176-1574
Current Organisation
University of Western Australia
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Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.NPEP.2005.11.006
Abstract: Using radioactive in situ hybridisation, the distribution of prodynorphin mRNA in the brains of C57Bl/6 mice was systemically investigated, and double-labelling in situ hybridisation was used to determine the extent to which neuropeptide Y (NPY) and prodynorphin mRNAs were co-expressed. Our results demonstrate that prodynorphin mRNA expression in the mouse brain is localised at specific subregions of the olfactory bulb, cortex, hippoc us, amygdala, basal ganglia, thalamus, hypothalamus, mesencephalon and myelencephalon. Among the regions displaying the most intense labelling were the olfactory tubercle, lateral septum (LS), caudate putamen (Cpu), central amygdaloid nucleus (Ce), paraventricular hypothalamic nucleus (PVN), supraoptic nucleus (SO), lateral hypothalamic area (LHA), ventromedial hypothalamic nucleus (VMH), lateral reticular nucleus (LRt) and solitary tract nucleus (NTS). In the arcuate nucleus of the hypothalamus (Arc), double-labelling in situ hybridisation revealed that prodynorphin expressing neurons also contained NPY mRNA, with a co-localisation rate of approximately 88% in the lateral part of the Arc, and 79% in the dorsal part of the Arc, respectively, suggesting potential overlapping functions of these two neurotransmitters in feeding type behaviour.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2017
DOI: 10.1038/IJO.2017.79
Abstract: Obesity and eating disorders are often studied and treated separately. While the increases in obesity prevalence are well known, examination of its co-occurrence with eating disorders, a problem also of public health concern, is important because eating disorder behaviors are known to contribute to obesity onset and maintenance, and vice versa. Data from large cross-sectional representative statewide community s les of people in the years of 1995 (n=3001), 2005 (n=3047) and 2015 (n=3005) were analyzed. Data were collected using a structured, self-report interview that included demographic, health-related, weight, height and eating disorder behavior questions. Eating behavior questions assessed binge eating, very strict dieting/fasting and purging, and were derived from the Eating Disorder Examination. Logistic regression analyses were conducted comparing prevalence of obesity, eating disorder behaviors and their co-occurrence. The prevalence of obesity or binge eating, or obesity with comorbid binge eating, each increased significantly from 1995 to 2005 (P<0.001 for each comparison) and continued to increase significantly from 2005 to 2015 (P<0.001 for each comparison). The highest increases from 1995 to 2015 were in the prevalence of obesity with comorbid binge eating (7.3-fold), or obesity with comorbid very strict dieting/fasting (11.5-fold). The prevalence of very strict dieting/fasting also increased significantly from 1995 to 2015 (3.8-fold). The prevalence of purging, or obesity with comorbid purging, did not change significantly from 1995 to 2015. There were statewide increases during the 20 years from 1995 to 2015 in the independent prevalence of obesity, binge eating and very strict dieting/fasting, and even higher increases in the prevalence of obesity with comorbid binge eating, and obesity with comorbid very strict dieting/fasting. These findings support the need for more integrated approaches to both the prevention and treatment of obesity and eating disorder behaviors, namely binge eating and very strict dieting/fasting.
Publisher: Oxford University Press (OUP)
Date: 22-09-2011
DOI: 10.1093/NDT/GFR575
Abstract: Elevated macrophage inhibitory cytokine-1 (MIC-1/GDF15) levels in serum mediate anorexia and weight loss in some cancer patients and similarly elevated levels occur in chronic kidney disease (CKD). Serum MIC-1/GDF15 is also elevated in chronic inflammatory diseases and predicts atherosclerotic events independently of traditional risk factors. The relationship between chronic inflammation, decreasing body mass index (BMI) and increased mortality in CKD is not well understood and is being actively investigated. MIC-1/GDF15 may link these features of CKD. Cohorts of incident dialysis patients from Sweden (n = 98) and prevalent hemodialysis patients from the USA (n = 381) had serum MIC-1/GDF15, C-reactive protein (CRP) levels and BMI measured at study entry. Additional surrogate markers of nutritional adequacy, body composition and inflammation were assessed in Swedish patients. Patients were followed for all-cause mortality. In the Swedish cohort, serum MIC-1/GDF15 was associated with decreasing BMI, measures of nutrition and markers of oxidative stress and inflammation. Additionally, high serum MIC-1/GDF15 levels identified patients with evidence of protein-energy wasting who died in the first 3 years of dialysis. The ability of serum MIC-1/GDF15 to predict mortality in the first 3 years of dialysis was confirmed in the USA cohort. In both cohorts, serum MIC-1/GDF15 level was an independent marker of mortality when adjusted for age, CRP, BMI, history of diabetes mellitus and/or cardiovascular disease and glomerular filtration rate or length of time on dialysis at study entry. MIC-1/GDF15 is a novel independent serum marker of mortality in CKD capable of significantly improving the mortality prediction of other established markers. MIC-1/GDF15 may mediate protein-energy wasting in CKD and represent a novel therapeutic target for this fatal complication.
Publisher: MDPI AG
Date: 21-09-2016
DOI: 10.3390/HEALTHCARE4030071
Abstract: Very low energy diets (VLED) are efficacious in inducing rapid weight loss but may not contain adequate macronutrients or micronutrients for in iduals with varying nutritional requirements. Adequate protein intake during weight loss appears particularly important to help preserve fat free mass and control appetite, and low energy and carbohydrate content also contributes to appetite control. Therefore, the purpose of this study was to compare the nutritional content (with a focus on protein), nutritional adequacy and cost of all commercially-available VLED brands in Australia. Nutritional content and cost were extracted and compared between brands and to the Recommended Dietary Intake (RDI) or adequate intake (AI) of macronutrients and micronutrients for men and women aged 19-70 years or >70 years. There was wide variability in the nutritional content, nutritional adequacy and cost of VLED brands. Most notably, even brands with the highest daily protein content, based on consuming three products/day (KicStart™ and Optislim(®), ~60 g/day), only met estimated protein requirements of the smallest and youngest women for whom a VLED would be indicated. Considering multiple options to optimise protein content, we propose that adding pure powdered protein is the most suitable option because it minimizes additional energy, carbohydrate and cost of VLEDs.
Publisher: Elsevier BV
Date: 04-2015
Abstract: Previously published research that examined the effects of high egg consumption in people with type 2 diabetes (T2D) produced conflicting results leading to recommendations to limit egg intake. However, people with T2D may benefit from egg consumption because eggs are a nutritious and convenient way of improving protein and micronutrient contents of the diet, which have importance for satiety and weight management. In this randomized controlled study, we aimed to determine whether a high-egg diet (2 eggs/d for 6 d/wk) compared with a low-egg diet (<2 eggs/wk) affected circulating lipid profiles, in particular high-density lipoprotein (HDL) cholesterol, in overweight or obese people with prediabetes or T2D. A total of 140 participants were randomly assigned to one of the 2 diets as part of a 3-mo weight maintenance study. Participants attended the clinic monthly and were instructed on the specific types of foods and quantities to be consumed. There was no significant difference in the change in HDL cholesterol from screening to 3 mo between groups the mean difference (95% CI) between high- and low-egg groups was +0.02 mmol/L (-0.03, 0.08 mmol/L P = 0.38). No between-group differences were shown for total cholesterol, low-density lipoprotein cholesterol, triglycerides, or glycemic control. Both groups were matched for protein intake, but the high-egg group reported less hunger and greater satiety postbreakfast. Polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) intakes significantly increased from baseline in both groups. High egg consumption did not have an adverse effect on the lipid profile of people with T2D in the context of increased MUFA and PUFA consumption. This study suggests that a high-egg diet can be included safely as part of the dietary management of T2D, and it may provide greater satiety. This trial was registered at the Australia New Zealand Clinical Trials Registry (www.anzctr.org.au/) as ACTRN12612001266853.
Publisher: Wiley
Date: 17-12-2020
DOI: 10.1111/OBR.13180
Abstract: Binge eating disorder (BED) is a public health problem in several countries. BED is commonly associated with comorbidities such as obesity, diabetes, and depression. Notwithstanding the health problems associated with BED, evidence‐based treatments for BED are not widely used by healthcare professionals worldwide. Thus, we provide an overview of the leading evidence‐based psychological therapies for BED, with the intention of informing healthcare professionals and the general community and facilitating greater provision of treatment. Cognitive behavior therapy (CBT) for BED is briefly presented, focusing mainly on adaptations and stages of the cognitive behavior therapy‐enhanced (CBT‐E) transdiagnostic model for eating disorders. We also succinctly discuss the use of CBT in combination with weight management interventions or pharmacotherapy, as well as the use of interpersonal therapy and dialectical behavior therapy for BED. We conclude that there is a variety of evidence‐based psychological therapies that can be used by a variety of healthcare professionals (not only by psychologists) to help reduce binge eating and associated psychopathology in people with BED. Given the high and increasing prevalence of BED, as well as the availability of effective evidence‐based treatments, we encourage more healthcare professionals to explore up‐skilling to assist people with BED.
Publisher: Walter de Gruyter GmbH
Date: 26-09-2016
Abstract: New evidence suggests that obesity is deleterious for bone health, and obesity treatments could potentially exacerbate this. This narrative review, largely based on recent systematic reviews and meta-analyses, synthesizes the effects on bone of bariatric surgery, weight loss pharmaceuticals and dietary restriction. All three obesity treatments result in statistically significant reductions in hip bone mineral density (BMD) and increases in bone turnover relative to pre-treatment values, with the reductions in hip BMD being strongest for bariatric surgery, notably Roux-en Y gastric bypass (RYGB, 8%–11% of pre-surgical values) and weakest for dietary restriction (1%–1.5% of pre-treatment values). Weight loss pharmaceuticals (orlistat or the glucagon-like peptide-1 receptor agonist, liraglutide) induced no greater changes from pre-treatment values than control, despite greater weight loss. There is suggestive evidence that liraglutide may increase bone mineral content (BMC) – but not BMD – and reduce fracture risk, but more research is required to clarify this. All three obesity treatments have variable effects on spine BMD, probably due to greater measurement error at this site in obesity, suggesting that future research in this field could focus on hip rather than spine BMD. Various mechanisms have been proposed for BMD loss with obesity treatments, notably reduced nutritional intake/absorption and insufficient exercise, and these are potential avenues for protection against bone loss. However, a pressing outstanding question is whether this BMD reduction contributes to increased fracture risk, as has been observed after RYGB, and whether any such increase in fracture risk outweighs the risks of staying obese (unlikely).
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.PEPTIDES.2006.07.031
Abstract: The gut-derived hormone peptide YY (PYY) is most commonly known for its effect on satiety, decreasing food intake and body weight in animals and humans. However, PYY is also involved in a wide range of digestive functions including regulating insulin secretion and glucose homeostasis. Over the last few years, there have been several interesting clinical and animal studies investigating the role of PYY in glucose homeostasis. This review aims to present an updated summary of findings over the last few decades highlighting the role of PYY in regulating insulin output and insulin sensitivity, and the potential mechanisms involved.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.MCE.2015.09.014
Abstract: Energy restriction induces physiological effects that hinder further weight loss. Thus, deliberate periods of energy balance during weight loss interventions may attenuate these adaptive responses to energy restriction and thereby increase the efficiency of weight loss (i.e. the amount of weight or fat lost per unit of energy deficit). To address this possibility, we systematically searched MEDLINE, PreMEDLINE, PubMed and Cinahl and reviewed adaptive responses to energy restriction in 40 publications involving humans of any age or body mass index that had undergone a diet involving intermittent energy restriction, 12 with direct comparison to continuous energy restriction. Included publications needed to measure one or more of body weight, body mass index, or body composition before and at the end of energy restriction. 31 of the 40 publications involved 'intermittent fasting' of 1-7-day periods of severe energy restriction. While intermittent fasting appears to produce similar effects to continuous energy restriction to reduce body weight, fat mass, fat-free mass and improve glucose homeostasis, and may reduce appetite, it does not appear to attenuate other adaptive responses to energy restriction or improve weight loss efficiency, albeit most of the reviewed publications were not powered to assess these outcomes. Intermittent fasting thus represents a valid--albeit apparently not superior--option to continuous energy restriction for weight loss.
Publisher: American Diabetes Association
Date: 2002
DOI: 10.2337/DIABETES.51.1.152
Abstract: Increased hypothalamic neuropeptide-Y (NPY) action and disruption of the melanocortin (MC)-4 receptor both result in hyperphagia and obesity. To determine whether similar hormonal and metabolic mechanisms are involved in these two obesity syndromes, we investigated the time course of effects induced by 6-day intracerebroventricular (ICV) infusion of NPY (3.5 nmol/day) or the MC4 receptor antagonist HS014 (4.8 nmol/day) in rats pair-fed with vehicle-infused controls. The weight of white adipose tissue (WAT) deposits was increased after 6-day NPY and HS014 infusion compared with controls, and the increase was significantly greater in HS014- than in NPY-infused rats (retroperitoneal WAT: NPY 0.57 ± 0.05 HS014 0.80 ± 0.05 control 0.43 ± 0.03% body wt, n = 8–13, P & 0.05). Plasma leptin was also increased in both experimental groups (NPY 10.6 ± 1.9 HS014 4.4 ± 0.9 control 2.0 ± 0.1 ng/ml, n = 8–13, P & 0.05 for all comparisons). Basal plasma corticosterone and insulin levels were increased by ICV NPY infusion, whereas HS014-infused rats showed no significant increase in these parameters on any of 1–6 days of infusion. Both NPY and HS014 infusion potentiated intravenous glucose-induced (300 mg/kg) plasma insulin levels, and there was no difference in glycemia among groups. In NPY-infused rats, the plasma free fatty acid levels were decreased and triglyceridemia was increased compared with controls, but these parameters were unchanged in HS014-infused rats. Hepatic triglyceride content was significantly increased by HS014 but not by NPY infusion. Levels of uncoupling protein-1 mRNA in brown adipose tissue were significantly decreased after 6 days of HS014 infusion, similar to the effect of central NPY. Because ICV HS014 induced at least as great an increase in fat mass as ICV NPY and yet had ergent hormonal and metabolic effects, we conclude that MC4 receptor antagonism does not induce obesity solely by regulation of the endogenous NPY-ergic system.
Publisher: Elsevier BV
Date: 05-2009
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.NPEP.2007.11.003
Abstract: The gut-derived hormone, peptide YY (PYY) reduces food intake and enhances satiety in both humans and animals. Obese in iduals also have a deficiency in circulating peptide YY, although whether this is a cause or a consequence of obesity is unclear. Our aims were to determine whether peptide YY (PYY) over-expression may have therapeutic effects for the treatment of obesity by altering energy balance and glucose homeostasis. We generated PYY transgenic mice and measured body weight, food intake, temperature, adiposity, glucose tolerance, circulating hormone and lipid concentrations and hypothalamic neuropeptide levels (neuropeptide Y proopiomelanocortin, and thyrotropin-releasing hormone) under chow and high-fat feeding and after crossing these mice onto the genetically obese leptin-deficient ob/ob mouse background. PYY transgenic mice were protected against diet-induced obesity in association with increased body temperature (indicative of increased thermogenesis) and sustained expression of thyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus. Moreover, PYY transgenic mice crossed onto the genetically obese ob/ob background had significantly decreased weight gain and adiposity, reduced serum triglyceride levels and improved glucose tolerance compared to ob/ob controls. There was no effect of PYY transgenic over expression on basal or fasting-induced food intake measured at 11-12 weeks of age. Together, these findings suggest that long-term administration of PYY, PYY-like compounds or agents that stimulate PYY synthesis in vivo can reduce excess adiposity and improve glucose tolerance, possibly via effects on the hypothalamo-pituitary-thyroid axis and thermogenesis.
Publisher: FapUNIFESP (SciELO)
Date: 02-2016
Publisher: Wiley
Date: 30-07-2010
DOI: 10.1002/JBMR.61
Abstract: The neuropeptide Y (NPY) system has been implicated in the regulation of bone homeostasis and osteoblast activity, but the mechanism behind this is unclear. Here we show that Y1 receptor signaling is directly involved in the differentiation of mesenchymal progenitor cells isolated from bone tissue, as well as the activity of mature osteoblasts. Importantly, the mRNA levels of two key osteogenic transcription factors, runx2 and osterix, as well as the adipogenic transcription factor PPAR-gamma, were increased in long bones of Y1(-/-) mice compared with wild-type mice. In vitro, bone marrow stromal cells (BMSCs) isolated from Y1(-/-) mice formed a greater number of mineralized nodules under osteogenic conditions and a greater number of adipocytes under adipogenic conditions than controls. In addition, both the number and size of fibroblast colony-forming units formed in vitro by purified osteoprogenitor cells were increased in the absence of the Y1 receptors, suggestive of enhanced proliferation and osteogenesis. Furthermore, the ability of two specific populations of mesenchymal progenitor cells isolated from bone tissue, an immature mesenchymal stem cell population and a more committed osteoprogenitor cell population, to differentiate into osteoblasts and adipocytes in vitro was enhanced in the absence of Y1 receptor signaling. Finally, Y1 receptor deletion also enhanced the mineral-producing ability of mature osteoblasts, as shown by increased in vitro mineralization by BMSCs isolated from osteoblast-specific Y1(-/-) mice. Together these data demonstrate that the NPY system, via the Y1 receptor, directly inhibits the differentiation of mesenchymal progenitor cells as well as the activity of mature osteoblasts, constituting a likely mechanism for the high-bone-mass phenotype evident in Y1(-/-) mice.
Publisher: Wiley
Date: 11-2011
DOI: 10.1038/OBY.2011.99
Abstract: Y2 receptors, particularly those in the brain, have been implicated in neuropeptide Y (NPY)-mediated effects on energy homeostasis and bone mass. Recent evidence also indicates a role for Y2 receptors in peripheral tissues in this process by promoting adipose tissue accretion however their effects on energy balance remain unclear. Here, we show that adult-onset conditional knockdown of Y2 receptors predominantly in peripheral tissues results in protection against diet-induced obesity accompanied by significantly reduced weight gain, marked reduction in adiposity and improvements in glucose tolerance without any adverse effect on lean mass or bone. These changes occur in association with significant increases in energy expenditure, respiratory exchange ratio, and physical activity and despite concurrent hyperphagia. On a chow diet, knockdown of peripheral Y2 receptors results in increased respiratory exchange ratio and physical activity with no effect on lean or bone mass, but decreases energy expenditure without effecting body weight or food intake. These results suggest that peripheral Y2 receptor signaling is critical in the regulation of oxidative fuel selection and physical activity and protects against the diet-induced obesity. The lack of effects on bone mass seen in this model further indicates that bone mass is primarily controlled by non-peripheral Y2 receptors. This study provides evidence that novel drugs that target peripheral rather than central Y2 receptors could provide benefits for the treatment of obesity and glucose intolerance without adverse effects on lean and bone mass, with the additional benefit of avoiding side effects often associated with pharmaceuticals that act on the central nervous system.
Publisher: The Endocrine Society
Date: 11-2006
DOI: 10.1210/EN.2006-0097
Abstract: Neuropeptide Y (NPY) is a key regulator of energy homeostasis and is implicated in the development of obesity and type 2 diabetes. Whereas it is known that hypothalamic administration of exogenous NPY peptides leads to increased body weight gain, hyperphagia, and many hormonal and metabolic changes characteristic of an obesity syndrome, the Y receptor(s) mediating these effects is disputed and unclear. To investigate the role of different Y receptors in the NPY-induced obesity syndrome, we used recombinant adeno-associated viral vector to overexpress NPY in mice deficient of selective single or multiple Y receptors (including Y1, Y2, and Y4). Results from this study demonstrated that long-term hypothalamic overexpression of NPY lead to marked hyperphagia, hypogonadism, body weight gain, enhanced adipose tissue accumulation, hyperinsulinemia, and other hormonal changes characteristic of an obesity syndrome. NPY-induced hyperphagia, hypogonadism, and obesity syndrome persisted in all genotypes studied (Y1−/−, Y2−/−, Y2Y4−/−, and Y1Y2Y4−/− mice). However, triple deletion of Y1, Y2, and Y4 receptors prevented NPY-induced hyperinsulinemia. These findings suggest that Y1, Y2, and Y4 receptors under this condition are not crucially involved in NPY’s hyperphagic, hypogonadal, and obesogenic effects, but they are responsible for the central regulation of circulating insulin levels by NPY.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.NEULET.2012.03.024
Abstract: Stress plays a role in the development and severity of psychotic symptoms and there may be a genetic component to stress vulnerability in schizophrenia. Using an established mouse model for schizophrenia, we investigated the behavioural and endocrine response of Nrg1 transmembrane domain mutant mice (Nrg1 HET) and wild type-like (WT) littermates to acute restraint stress. Animals were screened at 3-4 months and 6-7 months of age (before and after onset of hyperlocomotion) for open field behaviour and serum corticosterone levels. In younger mice, stress reduced locomotive and explorative measures and increased anxiety-like behaviour regardless of genotype. Older Nrg1 mutants were less susceptible to the effects of stress on anxiety-related behaviours. All mice responded to restraint stress with robust increases in serum corticosterone. Importantly, the stress-induced increase in corticosterone was more pronounced in Nrg1 mutant than WT mice at the younger but not the older age. Our results suggest that transmembrane domain Nrg1 has only a moderate effect on the acute stress response of mice. The behavioural differences detected between WT and Nrg1 HET mice at the older age were evident without parallel modifications to the glucocorticoid system.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2010
DOI: 10.1038/IJO.2009.232
Abstract: Neuropeptide Y and its Y receptors are important players in the regulation of energy homeostasis. However, while their functions in feeding regulation are well recognized, functions in other critical aspects of energy homeostasis are largely unknown. To investigate the function of Y1 receptors in the regulation of energy homeostasis, we examined energy expenditure, physical activity, body composition, oxidative fuel selection and mitochondrial oxidative capacity in germline Y1(-/-) mice as well as in a conditional Y1-receptor-knockdown model in which Y1 receptors were knocked down in peripheral tissues of adult mice. Germline Y1(-/-) mice of both genders not only exhibit a decreased respiratory exchange ratio, indicative of increased lipid oxidation, but interestingly also develop late-onset obesity. However, the increased lipid oxidation is a primary effect of Y1 deletion rather than secondary to increased adiposity, as young Y1(-/-) mice are lean and show the same effect. The mechanism behind this is likely because of increased liver and muscle protein levels of carnitine palmitoyltransferase-1 (CPT-1) and maximal activity of key enzymes involved in beta-oxidation beta-hydroxyacyl CoA dehydrogenase (betaHAD) and medium-chain acyl-CoA dehydrogenase (MCAD), leading to increased mitochondrial capacity for fatty acid transport and oxidation. These effects are controlled by peripheral Y1-receptor signalling, as adult-onset conditional Y1 knockdown in peripheral tissues also leads to increased lipid oxidation, liver CPT-1 levels and betaHAD activity. Importantly, these mice are resistant to diet-induced obesity. This work shows the primary function of peripheral Y1 receptors in the regulation of oxidative fuel selection and adiposity, opening up new avenues for anti-obesity treatments by targeting energy utilization in peripheral tissues rather than suppressing appetite by central effects.
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.NPEP.2006.08.002
Abstract: Low circulating peptide YY (PYY) levels are reported in obese and type II diabetic subjects and results from PYY knockout animals suggests that PYY deficiency may have a causative role in the etiology of obesity and type 2 diabetes. Here, our aims were to determine whether people with a genetic predisposition to developing type 2 diabetes and obesity differ from otherwise similar subjects without such family history, in fasting or meal-related PYY levels, fasting insulin, insulin secretion (HOMA-B) and insulin sensitivity. We also investigated whether PYY ablation affects the intrinsic ability of islets to secrete insulin, which may be a contributing factor to the hyperinsulinemia observed in PYY knockout mice. Healthy female first-degree relatives of people with type 2 diabetes were matched for age, gender and BMI to control subjects but had significantly lower insulin sensitivity (p<0.05). Relatives also had significantly lower fasting serum PYY levels than controls (p<0.05), but their PYY response to a high fat meal (4250 kJ, 73% fat) was not significantly different. Fasting PYY level correlated positively with glucose infusion rate (r=0.713, p=0.002) and fasting adiponectin (r=0.5, p=0.02). Islets of Langerhans from PYY knockout mice were found to hypersecrete insulin in response to 25 mM glucose (p<0.05). These data demonstrate that lack of PYY enhances insulin secretion from the Islets of Langerhans and that low fasting PYY levels are associated with insulin resistance in humans. Together, these findings suggest that low circulating levels of PYY could contribute to hyperinsulinemia and insulin resistance, and possibly contribute to subsequent development of obesity and type 2 diabetes.
Publisher: Public Library of Science (PLoS)
Date: 19-01-2016
Publisher: Frontiers Media SA
Date: 23-07-2021
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.BONE.2015.05.037
Abstract: Brown adipose tissue (BAT), largely controlled by the sympathetic nervous system (SNS), has the ability to dissipate energy in the form of heat through the actions of uncoupling protein-1 (UCP-1), thereby critically influencing energy expenditure. Besides BAT, the SNS also strongly influences bone, and recent studies have demonstrated a positive correlation between BAT activity and bone mass, albeit the interactions between BAT and bone remain unclear. Here we show that UCP-1 is critical for protecting bone mass in mice under conditions of permanent mild cold stress for this species (22°C). UCP-1
Publisher: BMJ
Date: 23-05-2022
DOI: 10.1136/ANNRHEUMDIS-2022-EULAR.811
Abstract: Overweight and obesity are associated with greater incidence and progression of the structural defects of knee osteoarthritis, but it is unknown if weight loss is of benefit. To describe the association between change in body mass index (BMI) and the incidence and progression of structural defects in knee osteoarthritis. Scores from radiographic analyses of knees at baseline and at 4 to 5 years’ follow up were obtained from three independent data sets (the OAI and MOST data sets from the United States from America, and the CHECK data set from the Netherlands). The exposure of interest was change in BMI from baseline to 4 to 5 years’ follow up. To investigate the incidence of structural defects of knee osteoarthritis, we selected a total of 9732 knees (from 5802 participants) that had a Kellgren-Lawrence (KL) grade of knee osteoarthritis at baseline of ‘none’ (0) or ‘doubtful’ (1) (the ‘incidence cohort’), and determined the odds of having a KL grade at follow-up of ‘minimal’ (2), ‘moderate’ (3), or ‘severe’ (4). To investigate progression, we selected a total of 6084 knees (from 3996 participants) that had a KL grade at baseline of ‘minimal’ (2), ‘moderate’ (3), or ‘severe’ (4) (the ‘progression cohort’), and determined the odds of increasing by 1 or more KL grades by follow up. The degradation of three in idual structural features of knee osteoarthritis (i.e., joint space narrowing, osteophytes on the femoral surface, and osteophytes on the tibial surface), on both the medial and lateral sides of the knee, were also investigated in both the incidence and progression cohorts. Here, degradation was defined as an increase by 1 or more Osteoarthritis Research Society International (OARSI) grades. Change in BMI was positively associated with both the incidence and progression of knee osteoarthritis, as defined by KL grade. Specifically, for each one-unit change in BMI, the adjusted odds ratio for incidence was 1.05 (95% confidence interval [CI] 1.02 to 1.09), and for progression, the same adjusted odds ratio and 95% CI was also observed. Change in BMI was also positively associated with degradation (i.e., narrowing) of joint space on the medial but not the lateral side of the knee, with an adjusted odds ratio of 1.08 (95% CI 1.04 to 1.12) in the ‘incidence cohort’ and 1.08 (95% CI 1.03 to 1.12) in the ‘progression cohort’. Degradation of the tibial and femoral surfaces (i.e., osteophytes) was also seen on the medial but not the lateral side of the knee, but only in one of the two cohorts investigated (the ‘incidence cohort’), with an adjusted odds ratio of 1.07 (95% CI 1.03 to 1.12) for osteophytes on the femoral surface, and 1.05 (95% CI 1.01 to 1.09) for osteophytes on the tibial surface. Each one-unit reduction in BMI is associated with a 5 to 8% decrease in the odds of the incidence and progression of the structural defects of knee osteoarthritis, with lower odds of structural degradation specific to the medial – not lateral – side of the knee. We acknowledge the provision of datasets and/or research tools from three studies: the Osteoarthritis Initiative (OAI) Study the Multicenter Osteoarthritis Study (MOST) and the Cohort Hip and Cohort Knee (CHECK) Study. OAI is a collaborative informatics system created by the National Institute of Mental Health and the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) to provide a worldwide resource to quicken the pace of biomarker identification, scientific investigation and OA drug development. The OAI data repository is housed within the National Institute of Mental Health (NIMH) Data Archive (NDA). For the MOST data set, we wish to acknowledge the contributions of the study participants, investigators and research staff involved. MOST is comprised of four (4) cooperative grants: U01 AG18820 David T. Felson (Boston University) U01 AG18832 James Torner (University of Iowa) U01 AG18947 Cora E. Lewis (University of Alabama at Birmingham) U01 AG19069 Michael C. Nevitt (University of California, San Francisco), funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by MOST investigators. This manuscript was prepared using MOST data and does not claim, infer, or imply endorsement by MOST, by the MOST investigators and their respective institutions or by the University of California of the Data Recipients’ use of the Data, of the entity or personnel conducting the research, or of any results of the research. The CHECK study is funded by the Dutch Arthritis Foundation. Involved are: Erasmus Medical Center Rotterdam Kennemer Gasthuis Haarlem Leiden University Medical Center Maastricht University Medical Center Martini Hospital Groningen /Allied Health Care Center for Rheumatology and Rehabilitation Groningen Medical Spectrum Twente Enschede /Ziekenhuisgroep Twente Almelo Reade Center for Rehabilitation and Rheumatology St.Maartens-kliniek Nijmegen University Medical Center Utrecht and Wilhelmina Hospital Assen. Zubeyir Salis: None declared, Helen Keen: None declared, Blanca Gallego: None declared, Tuan van Nguyen: None declared, Amanda Sainsbury Speakers bureau: ZS and AS own 50% each of the shares in Zuman International, which receives royalties for books AS has written and payments for presentations, and provides paid training for higher degree students. AS additionally reports receiving presentation fees and travel reimbursements from Eli Lilly and Co, the Pharmacy Guild of Australia, Novo Nordisk, the Dietitians Association of Australia, Shoalhaven Family Medical Centres, the Pharmaceutical Society of Australia, and Metagenics, and serving on the Nestlé Health Science Optifast VLCD advisory board from 2016 to 2018., Consultant of: ZS and AS own 50% each of the shares in Zuman International, which receives royalties for books AS has written and payments for presentations, and provides paid training for higher degree students. AS additionally reports receiving presentation fees and travel reimbursements from Eli Lilly and Co, the Pharmacy Guild of Australia, Novo Nordisk, the Dietitians Association of Australia, Shoalhaven Family Medical Centres, the Pharmaceutical Society of Australia, and Metagenics, and serving on the Nestlé Health Science Optifast VLCD advisory board from 2016 to 2018.
Publisher: MDPI AG
Date: 10-01-2022
Abstract: Severely energy-restricted diets (SERDs) are an effective treatment for obesity, however, adherence to such diets is often perceived as poor by healthcare professionals. This investigation evaluated adherence to a 12-week SERD in participants with class II and III obesity. Reported food consumption was compared against in idualised SERD prescriptions. Body weight measures were obtained at baseline, 12 and 52 weeks. The data were analysed in three groups (i) the entire cohort (n = 26), (ii) completers (n = 13) and (iii) non-completers (n = 13). SERD prescription elements included (i) the number of meal replacement products (ii) total protein (iii) total energy intake (iv) level of dietary energy restriction (v) vegetable serves (vi) water serves, and (vii) how much physical activity was performed. A generalised repeated-measures mixed-effects model was used to investigate if adherence to the program elements in idually, or collectively, influenced weight loss. Completers had an average (± SD) of 4549 ± 748 kJ energy intake per day, resulting in a mean energy restriction of 62% compared to the 69% prescribed, indicating a degree of non-adherence. The percent weight changes for completers and non-completers were −7.8 ± 4.7% and −1.6 ± 2.6% at 12 weeks, and −12.2 ± 12.1% and −1.8 ± 3.2% at 52 weeks, respectively. Complete dietary adherence to a SERD may not be necessary to achieve a clinically relevant weight loss of 12% at 52 weeks, if energy is restricted by at least 62% (~4600 kJ per day) relative to requirements.
Publisher: Elsevier BV
Date: 10-1992
DOI: 10.1016/0005-2760(92)90298-A
Abstract: Hydrolysis by endothelial lipases of triacylglycerol-rich lipoproteins of diabetic origin were compared to lipoproteins of non-diabetic origin. The plasma lipoprotein fraction of density < 1.006 g/ml, including chylomicrons and VLDL, were incubated in vitro with post-heparin plasma (PHP) lipases. The lipoproteins of diabetic origin were hydrolysed at a significantly slower rate than lipoproteins from normal rats by the lipoprotein lipase component of PHP. However, if rats were fasted for 16 h prior to lipoprotein recovery, no differences in rates of VLDL hydrolysis were observed. Slower hydrolysis of lipoproteins of diabetic origin reflected a decrease in the apolipoprotein CII/CIII ratio and other changes in the apolipoprotein profile. To assess whether diabetic rats were less able to clear triacylglycerol independent of changes in the nature of the lipoproteins, we monitored the clearance of chylomicron-like lipid emulsions in hepatectomized rats. In vivo, emulsion triacylglycerol hydrolysis was not slowed due to diabetes. However, control and diabetic rats, which had been fasted for 16 h, cleared triacylglycerol at about twice the rate of fed rats. Triacylglycerol secretion rates in diabetic and control rats were similar, whether fed or fasted. We conclude that in streptozocin diabetic rats, hypertriglyceridemia was not due to overproduction of chylomicron- or VLDL-triacylglycerol, nor to decreased endothelial lipase activities. Rather, in fed diabetic rats, the triacylglycerol-rich lipoproteins are poorer substrates for lipoprotein lipase. This may lead to slower formation of remnants which would exacerbate slow remnant removal. VLDL of diabetic origin were hydrolysed as efficiently as VLDL from control donors, suggesting that in the fed state the lipolytic defect may be specific for chylomicrons.
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.BONE.2012.03.020
Abstract: The neuropeptide Y system has emerged as one of the major neural signalling pathways regulating bone homeostasis. Absence of Y1 receptor signalling from bone forming osteoblasts is responsible for an enhancement on bone mass in mice, suggesting that pharmacological blockade of Y1 receptors may offer a novel anabolic treatment option for improving bone mass. Here we show that oral administration of the selective Y1 receptor antagonist BIBO3304 for 8 weeks dose-dependently increases bone mass in mice. Histomorphometric analysis revealed a significant 1.5-fold increase in cancellous bone volume in the femora of mice treated with BIBO3304. Furthermore, bone microarchitecture was improved, with greater trabecular number and trabecular thickness. This increase in bone mass was associated with a significant increase in bone anabolic activity of osteoblasts and, interestingly, was evident despite a coincident increase in bone resorption, as evidenced by an increase in the number of the osteolytic osteoclasts. Changes were also evident in cortical bone, with a significant increase in periosteal mineral apposition rate. Importantly, no adverse extra-skeletal side effects were observed through Y1 receptor antagonism over the 8-week treatment period, with no effects of even the higher BIBO3304 dose on body weight, adiposity, energy metabolism or circulating corticosterone levels. Taken together, this work describes the first NPY-based anabolic treatment for improving bone mass, and highlights the therapeutic potential of blocking Y1 receptor signalling for the prevention of, or recovery from, degenerative skeletal diseases.
Publisher: Frontiers Media SA
Date: 06-2021
Abstract: Background: Previous studies have shown an increase in hunger during weight-loss maintenance (WLM) after diet-induced weight loss. Whether a combination of a higher protein, lower glycemic index (GI) diet and physical activity (PA) can counteract this change remains unclear. Aim: To compare the long-term effects of two diets [high protein (HP)-low GI vs. moderate protein (MP)-moderate GI] and two PA programs [high intensity (HI) vs. moderate intensity (MI)] on subjective appetite sensations during WLM after ≥8% weight loss (WL). Methods: Data derived from the 3-years PREVIEW randomized intervention study. An 8-weeks WL phase using a low-energy diet was followed by a 148-weeks randomized WLM phase. For the WLM phase, participants were assigned to one of the four groups: HP-MI, HP-HI, MP-MI, and MP-HI. Available data from 2,223 participants with overweight or obesity (68% women BMI ≥ 25 kg/m 2 ). Appetite sensations including satiety, hunger, desire to eat, and desire to eat something sweet during the two phases (at 0, 8 weeks and 26, 52, 104, and 156 weeks) were assessed based on the recall of feelings during the previous week using visual analogue scales. Differences in changes in appetite sensations from baseline between the groups were determined using linear mixed models with repeated measures. Results: There was no significant diet × PA interaction. From 52 weeks onwards, decreases in hunger were significantly greater in HP-low GI than MP-moderate GI ( P time × diet = 0.018, P dietgroup = 0.021). Although there was no difference in weight regain between the diet groups ( P time × diet = 0.630), hunger and satiety ratings correlated with changes in body weight at most timepoints. There were no significant differences in appetite sensations between the two PA groups. Decreases in hunger ratings were greater at 52 and 104 weeks in HP-HI vs. MP-HI, and greater at 104 and 156 weeks in HP-HI vs. MP-MI. Conclusions: This is the first long-term, large-scale randomized intervention to report that a HP-low GI diet was superior in preventing an increase in hunger, but not weight regain, during 3-years WLM compared with a MP-moderate GI diet. Similarly, HP-HI outperformed MP-HI in suppressing hunger. The role of exercise intensity requires further investigation. Clinical Trial Registration: www.ClinicalTrials.gov , identifier: NCT01777893.
Publisher: American Society for Clinical Investigation
Date: 05-2000
DOI: 10.1172/JCI8695
Publisher: Springer Science and Business Media LLC
Date: 17-08-2018
DOI: 10.1038/IJO.2017.206
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.NPEP.2014.03.001
Abstract: Orexigenic neuropeptide Y (NPY) and dynorphin (DYN) regulate energy homeostasis. Single NPY or dynorphin deletion reduces food intake or increases fat loss. Future developments of obesity therapeutics involve targeting multiple pathways. We hypothesised that NPY and dynorphin regulate energy homeostasis independently, thus double NPY and dynorphin ablation would result in greater weight and/or fat loss than the absence of NPY or dynorphin alone. We generated single and double NPY and dynorphin knockout mice (NPYΔ, DYNΔ, NPYDYNΔ) and compared body weight, adiposity, feeding behaviour, glucose homeostasis and brown adipose tissue uncoupling protein-1 (UCP-1) expression to wildtype counterparts. Body weight and adiposity were significantly increased in NPYDYNΔ, but not in NPYΔ or DYNΔ. This was not due to increased food intake or altered UCP-1 expression, which were not significantly altered in double knockouts. NPYDYNΔ mice demonstrated increased body weight loss after a 24-h fast, with no effect on serum glucose levels after glucose injection. Contrary to the predicted phenotype delineated from single knockouts, double NPY and dynorphin deletion resulted in heavier mice, with increased adiposity, despite no significant changes in food intake or UCP-1 activity. This indicates that combining long-term opioid antagonism with blockade of NPY-ergic systems may not produce anti-obesity effects.
Publisher: Wiley
Date: 26-09-2014
DOI: 10.1002/JBMR.2205
Abstract: Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress-induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress-induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6-week restraint, or cold-stress protocol, Npy-null mice exhibit three-fold greater bone loss compared to wild-type mice, owing to suppression of osteoblast activity. This stress-protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin-releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy-null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy-null mice blocks the increase in circulating noradrenaline and the stress-induced bone loss. Thus, NPY protects against excessive stress-induced bone loss, through Y2 receptor-mediated modulation of central and peripheral noradrenergic neurons.
Publisher: MDPI AG
Date: 21-02-2022
DOI: 10.3390/HEALTHCARE10020404
Abstract: Introduction: Overweight and obesity are the leading contributors to non-fatal burden of disease in Australia. Very low energy diets (VLEDs) comprising of meal replacement products (MRP) effectively induce substantial weight loss in people with obesity, yet they are rarely used as a first line treatment. Dietitians in private practice are perfectly placed to administer treatments for obesity however, little is known about the preferred interventions used or their attitudes to incorporating VLEDs and MRPs into their treatments for overweight and obesity. Methods: This study used descriptive qualitative methods to explore accredited practicing dietitians’ (APDs’) perspectives and practices regarding obesity and obesity interventions, including the use of VLEDs and MRPs. Qualitative in-depth semi-structured interviews were conducted with 20 dietitians who had experience in private practice and in treating obesity. Transcribed interviews were analysed thematically using the technique of template analysis. Results: In the context within which dietitians’ practice was found to be a barrier to using evidence-based practice (EBP) for obesity treatment, four overarching themes were found. These were: (1) patient-centred care is the dietitians’ preferred intervention model (2) VLEDs promote weight loss in specific situations (3) systemic barriers constrain effective dietetic practice and equitable access to all, and (4) successful outcomes are predicated on working outside of systemic barriers. Conclusion: Dietitians in private practice are well placed and able to provide life-enhancing and evidence-based treatments for overweight and obesity and associated chronic disease in the community. However, systemic barriers need to be addressed to provide equitable access to effective care irrespective of socio-economic status.
Publisher: Wiley
Date: 16-06-2015
DOI: 10.1002/JBMR.2564
Abstract: Diet-induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta-analysis (using a random-effects model) to quantify the effect of diet-induced weight loss on bone. We included 41 publications involving overweight or obese but otherwise healthy adults who followed a dietary weight-loss intervention. The primary outcomes examined were changes from baseline in total hip, lumbar spine, and total body bone mineral density (BMD), as assessed by dual-energy X-ray absorptiometry (DXA). Secondary outcomes were markers of bone turnover. Diet-induced weight loss was associated with significant decreases of 0.010 to 0.015 g/cm(2) in total hip BMD for interventions of 6, 12, or 24 (but not 3) months' duration (95% confidence intervals [CIs], -0.014 to -0.005, -0.021 to -0.008, and -0.024 to -0.000 g/cm(2), at 6, 12, and 24 months, respectively). There was, however, no statistically significant effect of diet-induced weight loss on lumbar spine or whole-body BMD for interventions of 3 to 24 months' duration, except for a significant decrease in total body BMD (-0.011 g/cm(2) 95% CI, -0.018 to -0.003 g/cm(2)) after 6 months. Although no statistically significant changes occurred in serum concentrations of N-terminal propeptide of type I procollagen (P1NP), interventions of 2 or 3 months in duration (but not of 6, 12, or 24 months' duration) induced significant increases in serum concentrations of osteocalcin (0.26 nmol/L 95% CI, 0.13 to 0.39 nmol/L), C-terminal telopeptide of type I collagen (CTX) (4.72 nmol/L 95% CI, 2.12 to 7.30 nmol/L) or N-terminal telopeptide of type I collagen (NTX) (3.70 nmol/L 95% CI, 0.90 to 6.50 nmol/L bone collagen equivalents [BCEs]), indicating an early effect of diet-induced weight loss to promote bone breakdown. These data show that in overweight and obese in iduals, a single diet-induced weight-loss intervention induces a small decrease in total hip BMD, but not lumbar spine BMD. This decrease is small in comparison to known metabolic benefits of losing excess weight.
Publisher: American Diabetes Association
Date: 12-1995
Publisher: Public Library of Science (PLoS)
Date: 30-12-2009
Publisher: Elsevier BV
Date: 05-2009
Publisher: Elsevier BV
Date: 03-2001
DOI: 10.1016/S0196-9781(01)00342-4
Abstract: Neuropeptide Y (NPY) in the hypothalamus exerts multiple physiological functions including stimulation of adipogenic pathways such as feeding and insulin secretion as well as inhibition of the somatotropic and gonadotropic axes. Since hypothalamic NPY-ergic activity is increased by negative energy balance, NPY enables coordinated regulation of growth and reproduction in parallel with energy availability. Chronic pathological increases in central NPY-ergic activity contribute to obesity. Many of the adipogenic effects of NPY are specifically dependent on adrenal glucocorticoids. However, in the current study we show that central NPY does not require adrenal hormones to inhibit the somatotropic and gonadotropic axes in rats. Male adrenalectomized and sham-operated normal rats were intracerebroventricularly (ICV) infused with NPY (15 microg/day) or saline for 5-7 days, and plasma leptin, insulin-like growth factor (IGF-1) and testosterone were assayed, and epididymal white adipose tissue (WATe) was weighed. In normal intact rats, WATe weight and leptinemia were significantly increased by NPY, and these effects were prevented by adrenalectomy. In normal rats, NPY markedly reduced plasma IGF-1 levels (470 +/- 40 versus 1260 +/- 90 ng/ml) and testosterone (0.53 +/- 0.28 versus 5.4 +/- 0.80 nmol/l in saline-infused controls, p < 0.0001). Adrenalectomy decreased plasma IGF-1 concentrations to 290 +/- 30 (p < 0.0001 versus normal rats), which were significantly reduced further by NPY. However, adrenalectomy had no significant effect on basal nor on NPY-induced plasma testosterone concentrations. In conclusion unlike the stimulatory effects of NPY on fat mass and leptinemia, NPY-induced inhibition of the somatotropic and gonadotropic axes in male rats do not require adrenal hormones.
Publisher: Public Library of Science (PLoS)
Date: 13-04-2012
Publisher: Springer Science and Business Media LLC
Date: 02-2000
Abstract: Primary ciliary dyskinesia (PCD), or immotile cilia syndrome (ICS), is an autosomal recessive disorder affecting ciliary movement with an incidence of 1 in 20000-30000. Dysmotility to complete immotility of cilia results in a multisystem disease of variable severity with recurrent respiratory tract infections leading to bronchiectasis and male subfertility. Ultrastructural defects are present in ciliated mucosa and spermatozoa. Situs inversus (SI) is found in about half of the patients (Kartagener syndrome). We have collected s les from 61 European and North American families with PCD. A genome-wide linkage search was performed in 31 multiplex families (169 in iduals including 70 affecteds) using 188 evenly spaced (19cM average interval) polymorphic markers. Both parametric (recessive model) and non-parametric (identity by descent allele sharing) linkage analyses were used. No major locus for the majority of the families was identified, although the s le was powerful enough to detect linkage if 40% of the families were linked to one locus. These results strongly suggest extensive locus heterogeneity. Potential genomic regions harbouring PCD loci were localised on chromosomes 3p, 4q, 5p, 7p, 8q, 10p, 11q, 13q, 15q, 16p, 17q and 19q. Linkage analysis using PCD families with a dynein arm deficiency provided 'suggestive' evidence for linkage to chromosomal regions 8q, 16pter, while analyses using only PCD families with situs inversus resulted in 'suggestive' scores for chromosomes 8q, and 19q.
Publisher: Springer Science and Business Media LLC
Date: 11-1997
Abstract: Neuropeptide Y in the hypothalamus is a potent physiological stimulator of feeding, and may contribute to the characteristic metabolic defects of obesity when hypothalamic levels remain chronically elevated. Since corticosterone and insulin are important regulators of fuel metabolism, the longitudinal effects of chronic (6 days) intracerebroventricular infusion of neuropeptide Y in normal rats on the hypothalamo-pituitary-adrenal axis and on insulin secretion were studied. Neuropeptide Y-infused rats were either allowed to eat ad libitum, or were pair-fed with normophagic control rats. Neuropeptide Y increased the basal plasma concentrations of adrenocorticotropic hormone and corticosterone during the first 2 days of its intracerebroventricular infusion and increased cold stress-induced plasma adrenocorticotropic hormone concentrations. After 4-6 days of central neuropeptide Y infusion, however, basal plasma adrenocorticotropic hormone and corticosterone concentrations were no different from control values (except in ad libitum-fed rats in which corticosteronaemia remained elevated), they were unaffected by the stress of cold exposure, and the hypothalamic content of corticotropin-releasing factor immunoreactivity was significantly decreased. A state of hyperinsulinaemia was present throughout the 6 days of intracerebroventricular neuropeptide Y infusion, being more marked in the ad libitum-fed than in the pair-fed group. The proportions of insulin, proinsulin, and conversion intermediates in plasma and pancreas were unchanged. Hyperinsulinaemia of the pair-fed neuropeptide Y-infused rats was accompanied by muscle insulin resistance and white adipose tissue insulin hyperresponsiveness, as assessed by the in vivo uptake of 2-deoxyglucose. Finally, bilateral subdiaphragmatic vagotomy prevented both the basal and the marked glucose-induced hyperinsulinaemia of animals chronically infused with neuropeptide Y, demonstrating that central neuropeptide Y-induced hyperinsulinaemia is mediated by the parasympathetic nervous system.
Publisher: S. Karger AG
Date: 1996
DOI: 10.1159/000126972
Abstract: The effect of acute intracerebroventricular (i.c.v.) injection of neuropeptide Y (NPY) on basal and glucose- or arginine-stimulated insulinemia was studied in anesthetized and conscious rats. Basal insulinemia was not significantly increased relative to control values after NPY injection. The insulinemic response to an intravenous bolus of glucose or arginine was unaffected by prior NPY injection, glycemic profiles being identical in control and NPY-injected rats. Plasma NPY concentrations were double the corresponding control values at 20 min after i.c.v. NPY injection, but this difference was not statistically significant. Although peripheral NPY inhibits insulin secretion, these elevated plasma NPY concentrations occurred too late to explain the lack of effect of i.c.v. NPY on substrate-induced insulin secretion. Compared to control rats, marked increases in corticosteronemia were observed after i.c.v. NPY injection in conscious animals. When allowed to eat ad libitum at the end of each experiment, NPY-injected rats consumed significantly more chow in 20 min than controls. We conclude that although acute i.c.v. injection of a maximum dose of NPY had definite effects on plasma corticosterone concentrations and feeding, it favored neither the basal nor the substrate-induced insulin output.
Publisher: Public Library of Science (PLoS)
Date: 24-07-2015
Publisher: Wiley
Date: 04-2001
DOI: 10.1038/OBY.2001.33
Abstract: Glucocorticoids acting through the central nervous system are postulated to play a role in the hyperinsulinemia and increased adiposity of obesity. We investigated the role of parasympathetic activation in glucocorticoid-induced hyperinsulinemia. Plasma pancreatic polypeptide (PP) levels were used as an index of parasympathetic output. Insulinemia and plasma PP levels were measured basally and after intravenous glucose injection (300 mg/kg) in adrenalectomized male rats infused with dexamethasone (7.5 microg/kg per day) intracerebroventricularly (ICV) or subcutaneously (SC) for 3 to 6 days in the presence or absence of acute atropine blockade (1.0 mg/kg). Food intake was controlled between groups. Compared with normal rats, adrenalectomy decreased white adipose tissue depot weights and leptinemia, and these were restored to normal values by ICV but not SC dexamethasone infusion. Adrenalectomy significantly reduced insulinemia below normal levels, which was restored by SC dexamethasone replacement. However, ICV dexamethasone replacement increased insulinemia of adrenalectomized rats to levels higher than normal control values (basal, 500 +/- 40 pM vs. 280 +/- 40 pM 1-minute postglucose, 2500 +/- 180 pM vs. 1240 +/- 260 pM p < 0.0001) and increased plasma PP levels, which were correlated with insulinemia. Atropine significantly reduced plasma insulin and PP to levels similar to normal controls but had no effect in any other group. These data show that glucocorticoids act within the brain to increase insulinemia, most likely through activation of parasympathetic efferent fibers. Such an affect would contribute to the adipogenic effects of central glucocorticoids.
Publisher: Wiley
Date: 02-02-2015
DOI: 10.1111/COB.12086
Abstract: The majority of weight loss studies fail to standardize conditions such as diet and exercise via a weight maintenance period prior to commencement of the trial. This study aimed to determine whether a weight stabilization period is necessary to establish stable baseline hormone concentrations. Fifty-one obese male participants with a body mass index of 30-40 kg m(-2) and aged 25-54 years underwent 4 weeks on an energy balance diet that was designed to achieve weight stability. Blood s les were collected in the fasting state at commencement and completion of the 4-week period, and circulating concentrations of 18 commonly measured hormones were determined. During the 4-week weight maintenance period, participants achieved weight stability within -1.5 ± 0.2 kg (-1.4 ± 0.2%) of their initial body weight. Significant reductions in serum insulin (by 18 ± 6.5%) and leptin (by 21 ± 6.0%) levels occurred, but no significant changes were observed for gut-derived appetite-regulating hormones (ghrelin and peptide YY), nor thyroid, adrenal, gonadal or somatotropic hormones. There were no significant correlations between the change in body weight and the change in circulating concentrations of insulin or leptin over the 4-week period, indicating that the observed changes were not due to weight loss, albeit significant negative correlations were observed between the changes in body weight and plasma ghrelin and peptide YY levels. This study demonstrates the need for baseline weight maintenance periods to stabilize serum levels of insulin and leptin in studies specifically investigating effects on these parameters in the obese. However, this does not apply to circulating levels of gut-derived appetite-regulating hormones (ghrelin and peptide YY), nor thyroid, adrenal, gonadal or somatotropic hormones.
Publisher: The Endocrine Society
Date: 05-2007
DOI: 10.1210/EN.2006-1408
Abstract: Neuropeptide Y, a neuropeptide abundantly expressed in the brain, has been implicated in the regulation of the hypothalamo-pituitary-somatotropic axis and the hypothalamo-pituitary-gonadotropic axis. Elevated hypothalamic neuropeptide Y expression, such as that occurs during fasting, is known to inhibit both of these axes. However, it is not known which Y receptor(s) mediate these effects. Here we demonstrate, using Y receptor knockout mice, that Y2 and Y4 receptors are separately involved in the regulation of these axes. Fasting-induced inhibition of hypothalamic GHRH mRNA expression and reduction of circulating IGF-I levels were observed in wild-type and Y4−/− mice but not Y2−/− or Y2−/−Y4−/− mice. In contrast, fasting-induced reduction of GnRH expression in the medial preoptic area and testis testosterone content were abolished in the absence of Y4 receptors. Colocalization of Y2 receptors and GHRH in the arcuate nucleus (Arc) suggests that GHRH mRNA expression in this region might be directly regulated by Y2 receptors. Indeed, hypothalamic-specific deletion of Y2 receptors in conditional knockout mice prevented the fasting-induced reduction in Arc GHRH mRNA expression. On the other hand, fasting-induced decrease in GnRH mRNA expression in the medial preoptic area is more likely indirectly influenced by Y4 receptors because no Y4 receptors could be detected on GnRH neurons in this region. Together these data show that fasting inhibits the somatotropic axis via direct action on Y2 receptors in the Arc and indirectly inhibits the gonadotropic axis via Y4 receptors.
Publisher: Public Library of Science (PLoS)
Date: 25-02-2021
DOI: 10.1371/JOURNAL.PONE.0247292
Abstract: Athletes undergoing energy restriction for weight/fat reduction sometimes apply ‘diet breaks’ involving increased energy intake, but there is little empirical evidence of effects on outcomes. Twenty-six resistance-trained athletes (11/26 or 42% female) who had completed 12 weeks of intermittent energy restriction participated in this study. Participants had a mean (SD) age of 29.3 (6.4) years, a weight of 72.7 (15.9) kg, and a body fat percentage of 21.3 (7.5) %. During the 1-week diet break, energy intake was increased (by means of increased carbohydrate intake) to predicted weight maintenance requirements. While the 1-week diet break had no significant effect on fat mass, it led to small but significant increases in mean body weight (0.6 kg, P .001), fat-free mass (0.7 kg, P .001) and in resting energy expenditure, from a mean (and 95% confidence interval) of 7000 (6420 to 7580) kJ/day to 7200 (6620 to 7780) kJ/day ( P = 0.026). Overall, muscle endurance in the legs (but not arms) improved after the diet break, including significant increases in the work completed by the quadriceps and hamstrings in a maximum-effort 25-repetition set, with values increasing from 2530 (2170 to 2890) J to 2660 (2310 to 3010) J ( P = 0.018) and from 1280 (1130 to 1430) J to 1380 (1220 to 1540) J ( P = 0.018) following the diet break, respectively. However, muscle strength did not change. Participants reported significantly lower sensations of hunger ( P = 0.017), prospective consumption ( P = 0.020) and irritability ( P = 0.041) after the diet break, and significantly higher sensations of fullness ( P = 0.002), satisfaction ( P = 0.002), and alertness ( P = 0.003). In summary, a 1-week diet break improved muscle endurance in the legs and increased mental alertness, and reduced appetite and irritability. With this considered, it may be wise for athletes to coordinate diet breaks with training sessions that require muscle endurance of the legs and/or mental focus, as well as in the latter parts of a weight loss phase when increases in appetite might threaten dietary adherence. Trial registration: Australian New Zealand Clinical Trials Registry Reference Number: ACTRN12618000638235 anzctr.org.au .
Publisher: Springer Science and Business Media LLC
Date: 11-2007
DOI: 10.1038/NM1677
Abstract: Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from in iduals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.
Publisher: Wiley
Date: 27-06-2011
Publisher: MDPI AG
Date: 07-09-2020
DOI: 10.3390/BS10090136
Abstract: Meal replacement product-based diets are an effective weight loss intervention used in the management of obesity. Historically, these diets have been underutilised by HealthCare Professionals (HCPs). An online survey of mixed methods design was distributed to HCPs to capture current perceptions and prescribing patterns of meal replacement products (MRPs) in the management of overweight and obesity. A total of 303 HCPs working in weight management across Australia began the survey and 197 (65%) completed it. While over 70% of HCPs have prescribed MRP currently or in the past, MRPs are only prescribed to a median 7% of patients seeking weight management treatment. Qualitative analysis identified potential barriers to MRP prescription, which include experience with patient non-compliance, perceived poor long-term weight loss durability and safety concerns regarding the product and its use as a total meal replacement program. Safety concerns are centred on the perceived risk of weight cycling and its potential negative psychological impact. MRP prescription is 66% more likely to occur if HCPs had formal training in the use of MRPs relative to those who did not, with a relative risk (RR) of 1.7 (95% CI 1.4, 2.0). This study highlights the potential barriers to the prescription of MRPs, which are centred around safety concerns. This also indicates that formal training may enhance the likelihood of prescribing MRPs, suggesting that once HCPs have a comprehensive understanding of the products and the evidence behind their use, their prescription is likely to be increased.
Publisher: Public Library of Science (PLoS)
Date: 29-06-2012
Publisher: American Diabetes Association
Date: 17-07-2013
DOI: 10.2337/DB12-1745
Abstract: Krüppel-like factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro. Here, we report that KLF3-null mice are lean and protected from diet-induced obesity and glucose intolerance. On a chow diet, plasma levels of leptin are decreased, and adiponectin is increased. Despite significant reductions in body weight and adiposity, wild-type and knockout animals show equivalent energy intake, expenditure, and excretion. To investigate the molecular events underlying these observations, we used microarray analysis to compare gene expression in Klf3+/+ and Klf3−/− tissues. We found that mRNA expression of Fam132a, which encodes a newly identified insulin-sensitizing adipokine, adipolin, is significantly upregulated in the absence of KLF3. We confirmed that KLF3 binds the Fam132a promoter in vitro and in vivo and that this leads to repression of promoter activity. Further, plasma adipolin levels were significantly increased in Klf3−/− mice compared with wild-type littermates. Boosting levels of adipolin via targeting of KLF3 offers a novel potential therapeutic strategy for the treatment of insulin resistance.
Publisher: MDPI AG
Date: 04-11-2014
DOI: 10.3390/NU6114856
Publisher: Springer Science and Business Media LLC
Date: 08-05-2013
DOI: 10.1038/IJO.2012.71
Abstract: Estrogen deficiency increases body weight or total and central adiposity and decreases energy expenditure. Hypothalamic neuropeptide Y (NPY) expression is altered by estrogen deficiency in rodents, but the long-term consequences on energy homeostasis are unknown. To investigate the role of NPY in the changes in energy expenditure and physical activity, as well as the associated changes in body weight and composition in response to short-term and long-term estrogen deficiency. Sham and ovariectomy (OVX) operations were performed at 8 weeks of age in wild-type (WT) and NPY(-/-) mice. Energy expenditure, physical activity, body composition and weight, as well as food intake were measured at 10-18 days (short-term) and 46-54 days (long-term) after OVX. OVX influences energy homeostasis differently at early compared with later time-points. At the early but not the late time point, OVX in WT mice reduced oxygen consumption and energy expenditure and tended to reduce resting metabolic rate. Interestingly, these effects of short-term estrogen deficiency were ablated by NPY deletion, with NPY(-/-) mice exhibiting significant increases in energy expenditure and resting metabolic rate. In addition to these hypermetabolic effects, OVX NPY(-/-) mice exhibited significantly lower body weight and whole-body fat mass relative to OVX WT controls at the short-term but not the long-term time point. Food intake and physical activity were unaltered by OVX, but NPY(-/-) mice exhibited significant reductions in these parameters relative to WT. The effects of estrogen deficiency to reduce energy metabolism are transient, and NPY is critical to this effect as well as the early OVX-induced obesity.
Publisher: LIDSEN Publishing Inc
Date: 21-02-2022
DOI: 10.21926/RPN.2202015
Abstract: We report the case of a 30-year-old male with significant obesity (body mass index 47 kg/m2) with co-existing moderate obstructive sleep apnoea, hypertension, hypercholesteremia and hypogonadotropic hypogonadism, who was treated with a very-low-energy diet (VLED) and lifestyle modification programme for 12 months. The patient lost weight throughout the entire treatment period (average weight loss was 2.1 kg/week, for a total of 42.7 kg), and showed marked improvement in co-morbidities and no adverse effects. This case demonstrates that prolonged (5-month) use of a VLED, under close medical supervision, is safe and effective in certain patients with obesity.
Publisher: Elsevier BV
Date: 02-2001
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.SLEH.2017.07.006
Abstract: Sleep is important for the physical, social and mental well-being of both children and adults. Over the years, there has been a general presumption that sleep will inevitably decline with the increase in technology and a busy 24-hour modern lifestyle. This narrative review discusses the empirical evidence for secular trends in sleep duration and the implications of these trends.
Publisher: Georg Thieme Verlag KG
Date: 12-1996
Abstract: Over the years, the work of research laboratories in Baton Rouge (USA), Seattle (USA) and Geneva (Switzerland) have reached analogous conclusions regarding the main etiology of obesity as studied in animals: it largely lies within the brain, notably within the hypothalamus. The hypothalamus is indeed known to modulate food intake and energy partitioning, while the periphery has also been proposed to feed-back on the central nervous system (CNS) to provide information on the state of body energy stores, the two together constituting a loop system connecting the brain to the periphery (1,2,3). This etiologic viewpoint of a pivotal role of the hypothalamus in obesity syndromes has been strengthened by the discovery of one hypothalamic neuropeptide and one peripheral (adipose tissue) hormone, respectively neuropeptide Y (4), and quite particularly, leptin (5). As neuropeptide Y produces hyperphagia (6, 7) and as leptin produces hypophagia in normal animals (8,9,10), the loop system just mentioned was thought to comprise functional relationships, at least between these two factors. Other evidence also suggested that such a loop system was altered in obese animals.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2011
Publisher: Springer Science and Business Media LLC
Date: 26-04-2023
DOI: 10.1186/S12874-023-01926-4
Abstract: Rheumatology researchers often categorize continuous predictor variables. We aimed to show how this practice may alter results from observational studies in rheumatology. We conducted and compared the results of two analyses of the association between our predictor variable (percentage change in body mass index [BMI] from baseline to four years) and two outcome variable domains of structure and pain in knee and hip osteoarthritis. These two outcome variable domains covered 26 different outcomes for knee and hip combined. In the first analysis (categorical analysis), percentage change in BMI was categorized as ≥ 5% decrease in BMI, 5% change in BMI, and ≥ 5% increase in BMI, while in the second analysis (continuous analysis), it was left as a continuous variable. In both analyses (categorical and continuous), we used generalized estimating equations with a logistic link function to investigate the association between the percentage change in BMI and the outcomes. For eight of the 26 investigated outcomes (31%), the results from the categorical analyses were different from the results from the continuous analyses. These differences were of three types: 1) for six of these eight outcomes, while the continuous analyses revealed associations in both directions (i.e., a decrease in BMI had one effect, while an increase in BMI had the opposite effect), the categorical analyses showed associations only in one direction of BMI change, not both 2) for another one of these eight outcomes, the categorical analyses suggested an association with change in BMI, while this association was not shown in the continuous analyses (this is potentially a false positive association) 3) for the last of the eight outcomes, the continuous analyses suggested an association of change in BMI, while this association was not shown in the categorical analyses (this is potentially a false negative association). Categorization of continuous predictor variables alters the results of analyses and could lead to different conclusions therefore, researchers in rheumatology should avoid it.
Publisher: American Diabetes Association
Date: 2006
DOI: 10.2337/DIABETES.55.01.06.DB05-0472
Abstract: Neuropeptide Y receptors are critical regulators of energy homeostasis, but the functional interactions and relative contributions of Y receptors and the environment in this process are unknown. We measured the effects of an ad libitum diet of normal or high-fat food on energy balance in mice with single, double, or triple deficiencies of Y1, Y2, or Y4 receptors. Whereas wild-type mice developed diet-induced obesity, Y2Y4 double knockouts did not. In contrast, Y1 knockout or Y1Y2 or Y1Y4 receptor double knockout mice developed an exacerbated diet-induced obesity syndrome. Remarkably, the antiobesity effect of Y2Y4 deficiency was stronger than the obesogenic effect of Y1 deficiency, since Y1Y2Y4 triple knockouts did not develop obesity on the high-fat diet. Resistance to diet-induced obesity in Y2Y4 knockouts was associated with reduced food intake and improved glucose tolerance in the absence of changes in total physical activity. Fecal concentration of free fatty acids was significantly increased in Y2Y4 knockouts in association with a significantly reduced bile acid pool and marked alterations in intestinal morphology. In addition, hypothalamic proopiomelanocortin expression was decreased in diet-induced obesity (in both wild-type and Y1 receptor knockout mice) but not in obesity-resistant Y2Y4 receptor knockout mice fed a high-fat diet. Therefore, deletion of Y2 and Y4 receptors synergistically protects against diet-induced obesity, at least partially via changes in food intake and hypothalamic proopiomelanocortin expression.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.ORCP.2016.01.001
Abstract: Text-message and e-mail are emerging as potential methods for improving weight outcomes among obese in iduals. The optimal volume, frequency, and timing of such interventions are unknown. This study investigated the effect of adjunct technological support on weight and psychological variables after a 3-month cognitive-behaviour therapy (CBT) group intervention. Sixty obese adults were randomised to a CBT programme plus intensive (text-message and e-mail CBT+ITS) or minimal (text-message only CBT+MTS) technological support. Assessments occurred at baseline, 3-, 6-, 9-, and 15-months. Outcome variables included weight (kg), body mass index (kg/m CBT+ITS (n=31) and CBT+MTS (n=29) participants lost 5.2% (±1.1) and 4.7% (±1.1) of their baseline weight by 3-months, 8.4% (±1.2) and 6.4% (±1.1) by 6-months, 9.6% (±1.3) and 6.4% (±1.3) by 9-months, and sustained a 7.5% (±1.3) and 5.1% (±1.3) loss at 15-months, respectively. There were no significant differences between intensive and minimal support, however, the CBT+ITS group showed a marginal advantage across all anthropometric measures. A low intensity text-message support programme is just as effective as higher intensity technological support for maintaining weight loss in obese adults. This represents a low-cost means of aiding weight loss maintenance without reliance on extended face-to-face treatment.
Publisher: Wiley
Date: 06-08-2014
DOI: 10.1111/OBR.12217
Abstract: This systematic review assessed the effect of weight loss in overweight and/or obese women undergoing assisted reproductive technology (ART) on their subsequent pregnancy outcome. Weight losses achieved by diet and lifestyle changes, very-low-energy diets, non-surgical medical interventions and bariatric surgery translated into significantly increased pregnancy rates and/or live birth in overweight and/or obese women undergoing ART in 8 of the 11 studies reviewed. In addition, regularization of the menstrual pattern, a decrease in cancellation rates, an increase in the number of embryos available for transfer, a reduction in the number of ART cycles required to achieve pregnancy and a decrease in miscarriage rates were reported. There were also a number of natural conceptions in five of the six studies that reported this outcome. Non-surgical medical weight loss procedures and bariatric surgery induced the greatest weight losses, but their use, as well as that of very-low-energy diets, for weight loss prior to ART requires careful consideration. While the overall quality of the studies included in this review was poor, these results support the clinical recommendation of advising overweight and/or obese women to lose weight prior to ART. Prospective randomized controlled trials are required to establish efficacious evidence-based guidelines for weight loss interventions in overweight and/or obese women prior to ART treatment.
Publisher: Cambridge University Press (CUP)
Date: 2016
DOI: 10.1017/JNS.2016.22
Abstract: Accurate estimation of food portion size is critical in dietary studies. Hands are potentially useful as portion size estimation aids however, their accuracy has not been tested. The aim of the present study was to test the accuracy of a novel portion size estimation method using the width of the fingers as a ‘ruler’ to measure the dimensions of foods (‘finger width method’), as well as fists and thumb or finger tips. These hand measures were also compared with household measures (cups and spoons). A total of sixty-seven participants (70 % female age 32·7 ( sd 13·7) years BMI 23·2 ( sd 3·5) kg/m 2 ) attended a 1·5 h session in which they estimated the portion sizes of forty-two pre-weighed foods and liquids. Hand measurements were used in conjunction with geometric formulas to convert estimations to volumes. Volumes determined with hand and household methods were converted to estimated weights using density factors. Estimated weights were compared with true weights, and the percentage difference from the true weight was used to compare accuracy between the hand and household methods. Of geometrically shaped foods and liquids estimated with the finger width method, 80 % were within ±25 % of the true weight of the food, and 13 % were within ±10 %, in contrast to 29 % of those estimated with the household method being within ±25 % of the true weight of the food, and 8 % being within ±10 %. For foods that closely resemble a geometric shape, the finger width method provides a novel and acceptably accurate method of estimating portion size.
Publisher: MDPI AG
Date: 20-11-2020
DOI: 10.3390/JFMK5040085
Abstract: C bell and colleagues recently published a randomised controlled trial investigating the effects of diets involving intermittent energy restriction versus continuous energy restriction on changes in body composition and resting metabolic rate (RMR) in resistance-trained adults[...]
Publisher: BMJ
Date: 10-2018
DOI: 10.1136/BMJSEM-2018-000423
Abstract: Reducing fat mass (FM) while retaining fat free mass (FFM) is a common goal of athletes. Evidence suggests that some—but not all—forms of intermittent energy restriction (IER) may be superior to the conventional method of continuous energy restriction (CER) for people with excess body fat that are sedentary, by reducing some of the adaptive responses to ER. However, it is yet to be established whether this dietary approach is effective for athletes. A single-blind, parallel group, randomised controlled trial with a 1:1 allocation ratio is proposed. Sixty healthy athletes aged ≥18 years will be recruited from local sporting facilities and randomised to an intervention of either moderate CER (mCER) or moderate IER (mIER). Both interventions will consist of 12 weeks of moderate ER, plus 3 weeks in energy balance (EB). The mCER intervention will entail 12 weeks of continuous moderate ER, followed by 3 weeks in EB. The mIER intervention will entail 12 weeks of moderate ER, administered as 4×3 week blocks of moderate ER, interspersed with 3×1 week blocks of EB. The co-primary outcomes are changes in FM and FFM after 12 weeks of moderate ER. Secondary outcomes will be changes in FM and FFM at 15 weeks after intervention commencement, as well as muscle performance, physical activity, sleep quality, changes in resting energy expenditure, subjective drive to eat, circulating concentrations of appetite-regulating hormones, mood states and diet acceptability. ACTRN12618000638235p.
Publisher: Wiley
Date: 10-11-2011
Publisher: Wiley
Date: 09-02-2017
DOI: 10.1111/NBU.12246
Publisher: The Endocrine Society
Date: 07-2007
DOI: 10.1210/ME.2006-0367
Abstract: Endogenous opioids, particularly dynorphins, have been implicated in regulation of energy balance, but it is not known how they mediate this in vivo. We investigated energy homeostasis in dynorphin knockout mice (Dyn−/− mice) and probed the interactions between dynorphins and the neuropeptide Y (NPY) system. Dyn−/− mice were no different from wild types with regards to body weight and basal and fasting-induced food intake, but fecal output was increased, suggesting decreased nutrient absorption, and they had significantly less white fat and lost more weight during a 24-h fast. The neuroendocrine and thermal responses to fasting were at least as pronounced in Dyn−/− as in wild types, and there was no stimulatory effect of dynorphin knockout on 24-h energy expenditure (kilocalories of heat produced) or physical activity. However, Dyn−/− mice showed increased circulating concentrations of 3,4-dihydroxyphenlacetic acid and 3,4-dihydroxyphenylglycol, suggesting increased activity of the sympathetic nervous system. The respiratory exchange ratio of male but not female Dyn−/− mice was reduced, demonstrating increased fat oxidation. Interestingly, expression of the orexigenic acting NPY in the hypothalamic arcuate nucleus was reduced in Dyn−/− mice. However, fasting-induced increases in pre-prodynorphin expression in the arcuate nucleus, the paraventricular nucleus, and the ventromedial hypothalamus but not the lateral hypothalamus were abolished by deletion of Y1 but not Y2 receptors. Therefore, ablation of dynorphins results in increases in fatty acid oxidation in male mice, reductions in adiposity, and increased weight loss during fasting, possibly via increases in sympathetic activity, decreases in intestinal nutrient absorption, and interactions with the NPYergic system.
Publisher: Elsevier BV
Date: 08-2006
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.MCE.2009.09.025
Abstract: Acute or long-term energy deficit in lean or obese rodents or humans stimulates food intake or appetite and reduces metabolic rate or energy expenditure. These changes contribute to weight regain in post-obese animals and humans. Some studies show that the reduction in metabolic rate with energy deficit in overweight people is transient. Energy restriction has been shown in some but not all studies to reduce physical activity, and this may represent an additional energy-conserving adaptation. Energy restriction up-regulates expression of the orexigenic neuropeptide Y, agouti related peptide and opioids and down-regulates that of the anorexigenic alpha-melanocyte stimulating hormone or its precursor pro-opioomelanocortin and the co-expressed cocaine and hetamine-regulated transcript in the arcuate nucleus of the hypothalamus. Recapitulating these hypothalamic changes in sated animals mimics the effects of energy deficit, namely increased food intake, reduced physical activity and reduced metabolic rate, suggesting that these energy-conserving adaptations are at least partially mediated by the hypothalamus.
Publisher: Wiley
Date: 31-05-2005
DOI: 10.1359/JBMR.050523
Publisher: MDPI AG
Date: 08-04-2019
DOI: 10.3390/BS9040036
Abstract: Obesity is a public health concern resulting in widespread personal, social, and economic burden. Many in iduals with obesity report feeling unable to stop eating or to control their food intake (i.e., a loss of control over eating) despite their best efforts. Experiencing loss of control over eating predicts further eating pathology and is a key feature of binge eating. Mindfulness (i.e., awareness and acceptance of current thoughts, feelings, sensations, and surrounding events) has emerged as a potential strategy to treat such eating disorder behaviors, but it is not known whether there is merit in investigating this strategy to address binge eating in postmenopausal women with obesity. Thus, this study aimed to examine the relationships between binge eating and mindfulness in postmenopausal women with obesity seeking weight loss treatment. Participants (n = 101) were assessed with the Eating Disorder Examination Questionnaire, the Loss of Control over Eating Scale, the Five-Facet Mindfulness Questionnaire, and the Langer Mindfulness Scale. Participants´ overall scores on both mindfulness scales were significantly and negatively correlated with binge eating frequency or the severity of loss of control over eating. Moreover, participants who reported fewer binge eating episodes were significantly more mindful than those who reported greater frequencies of binge eating episodes within the past 28 days. These findings suggest a merit in investigating the use of mindfulness-based therapies to treat binge eating in postmenopausal women with obesity.
Publisher: MDPI AG
Date: 11-07-2017
DOI: 10.3390/BS7030044
Abstract: Dietary interventions are the cornerstone of obesity treatment. The optimal dietary approach to weight loss is a hotly debated topic among health professionals and the lay public alike. An emerging body of evidence suggests that a higher level of adherence to a diet, regardless of the type of diet, is an important factor in weight loss success over the short and long term. Key strategies to improve adherence include designing dietary weight loss interventions (such as ketogenic diets) that help to control the increased drive to eat that accompanies weight loss, tailoring dietary interventions to a person’s dietary preferences (and nutritional requirements), and promoting self-monitoring of food intake. The aim of this paper is to examine these strategies, which can be used to improve adherence and thereby increase the success of dietary weight loss interventions.
Publisher: Wiley
Date: 29-04-2016
DOI: 10.1111/OBR.12422
Abstract: We conducted a systematic review and meta‐analysis to identify how diet‐induced weight loss in adults with overweight or obesity impacts on muscle strength. Twenty‐seven publications, including 33 interventions, most of which were 8–24 weeks in duration, were included. Meta‐analysis of seven interventions measuring knee extensor strength by isokinetic dynamometry in 108 participants found a significant decrease following diet‐induced weight loss (−9.0 [95% confidence interval: −13.8, −4.1] N/m, P 0.001), representing a 7.5% decrease from baseline values. Meta‐analysis of handgrip strength from 10 interventions in 231 participants showed a non‐significant decrease (−1.7 [−3.6, 0.1] kg, P = 0.070), with significant heterogeneity ( I 2 = 83.9%, P 0.001). This heterogeneity may have been due to diet type, because there was a significant decrease in handgrip strength in seven interventions in 169 participants involving moderate energy restriction (−2.4 [−4.8, −0.0] kg, P = 0.046), representing a 4.6% decrease from baseline values, but not in three interventions in 62 participants involving very‐low‐energy diet (−0.4 [−2.0, 1.2] kg, P = 0.610). Because of variability in methodology and muscles tested, no other data could be meta‐analyzed, and qualitative assessment of the remaining interventions revealed mixed results. Despite varying methodologies, diets and small s le sizes, these findings suggest a potential adverse effect of diet‐induced weight loss on muscle strength. While these findings should not act as a deterrent against weight loss, due to the known health benefits of losing excess weight, they call for strategies to combat strength loss – such as weight training and other exercises – during diet‐induced weight loss. © 2016 World Obesity
Publisher: Springer Science and Business Media LLC
Date: 18-03-2014
Publisher: Wiley
Date: 12-2018
DOI: 10.1111/OBR.12787
Abstract: Eating patterns involving intermittent energy restriction (IER) include 'intermittent fasting' where energy intake is severely restricted for several 'fasting' days per week, with 'refeeding' days (involving greater energy intake than during fasting days) at other times. Intermittent fasting does not improve weight loss compared to continuous energy restriction (CER), where energy intake is restricted every day. We hypothesize that weight loss from IER could be improved if refeeding phases involved restoration of energy balance (i.e. not ongoing energy restriction, as during intermittent fasting). There is some evidence in adults with overweight or obesity showing that maintenance of a lower weight may attenuate (completely or partially) some of the adaptive responses to energy restriction that oppose ongoing weight loss. Other studies show some adaptive responses persist unabated for years after weight loss. Only five randomized controlled trials in adults with overweight or obesity have compared CER with IER interventions that achieved energy balance (or absence of energy restriction) during refeeding phases. Two reported greater weight loss than CER, whereas three reported similar weight loss between interventions. While inconclusive, it is possible that achieving energy balance (i.e. avoiding energy restriction or energy excess) during refeeding phases may be important in realizing the potential of IER.
Publisher: Wiley
Date: 21-03-2012
DOI: 10.1111/J.1463-1326.2012.01592.X
Abstract: Both the neuronal-derived neuropeptide Y (NPY) and the gut hormone peptide YY (PYY) have been implicated in the regulation of energy balance and glucose homeostasis. However, despite similar affinities for the same Y receptors, the co-ordinated actions of these two peptides in energy and glucose homeostasis remain largely unknown. To investigate the mechanisms and possible interactions between PYY with NPY in the regulation of these processes, we utilized NPY/PYY single and double mutant mouse models and examined parameters of energy balance and glucose homeostasis. PYY(-/-) mice exhibited increased fasting-induced food intake, enhanced fasting and oral glucose-induced serum insulin levels, and an impaired insulin tolerance, - changes not observed in NPY(-/-) mice. Interestingly, whereas PYY deficiency-induced impairment in insulin tolerance remained in NPY(-/-) PYY(-/-) mice, effects of PYY deficiency on fasting-induced food intake and serum insulin concentrations at baseline and after the oral glucose bolus were absent in NPY(-/-) PYY(-/-) mice, suggesting that NPY signalling may be required for PYY's action on insulin secretion and fasting-induced hyperphagia. Moreover, NPY(-/-) PYY(-/-) , but not NPY(-/-) or PYY(-/-) mice had significantly decreased daily food intake, indicating interactive control by NPY and PYY on spontaneous food intake. Furthermore, both NPY(-/-) and PYY(-/-) mice showed significantly reduced respiratory exchange ratio during the light phase, with no additive effects observed in NPY(-/-) PYY(-/-) mice, indicating that NPY and PYY may regulate oxidative fuel selection via partly shared mechanisms. Overall, physical activity and energy expenditure, however, are not significantly altered by NPY and PYY single or double deficiencies. These findings show significant and erse interactions between NPY and PYY signalling in the regulation of different aspects of energy balance and glucose homeostasis.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.APPET.2018.06.029
Abstract: Disordered eating behaviors and cognitions have been extensively examined in s les of in iduals with eating disorders, as well as in non-clinical s les. However, such examinations are lacking in the general population. We investigated disordered eating behaviors and cognitions in a community representative s le of 6052 participants in South Australia, aged 15-99 years. Participants were interviewed regarding weight/shape overvaluation, strict dieting, binge eating, purging, low mood and body mass index (BMI). Linear and logistic regression analyses were used to estimate the direct effects between these features. Steiger's Z test was used to compare the difference between the semi-partial associations of low mood and strict dieting with binge eating. Our findings suggest that similar relationships between strict dieting, low mood, purging and binge eating to those shown in the trans-diagnostic cognitive-behavioral model of eating disorders in clinical s les occur in the general community. However, in the general population, strict dieting was associated with elevated BMIs (and not with low BMIs as predicated by the model). Although this study does not ascertain any causal relationships in the observed associations, public health messages or services for weight reduction in people with higher body weights could potentially benefit from integration with messages addressing mood disorders and purging, in order to reduce potential adverse effects on disordered eating behaviors.
Publisher: Springer Science and Business Media LLC
Date: 25-01-2020
DOI: 10.1007/S40519-020-00846-2
Abstract: The association between binge eating and obesity is increasing. Treatments for disorders of recurrent binge eating comorbid with obesity reduce eating disorder (ED) symptoms, but not weight. This study investigated the efficacy and safety of introducing a weight loss intervention to the treatment of people with disorders of recurrent binge eating and a high body mass index (BMI). A single-blind randomized controlled trial selected adults with binge eating disorder or bulimia nervosa and BMI ≥ 27 to < 40 kg/m Ninety-eight participants were randomized to the Health Approach to Weight Management and Food in Eating Disorders (HAPIFED) or to the Cognitive Behavioural Therapy-Enhanced (CBT-E). No between-group differences were found for percentage of participants achieving weight loss or secondary outcomes, except for reduction of purging behaviour, which was greater with HAPIFED (p = 0.016). Binge remission rates specifically at 12-month follow-up favoured HAPIFED (34.0% vs 16.7% p = 0.049). Overall, significant improvements in the reduction of ED symptoms were seen in both groups and these were sustained at the 12-month follow-up. HAPIFED was not superior to CBT-E in promoting clinically significant weight loss and was not significantly different in reducing most ED symptoms. No harm was observed with HAPIFED, in that no worsening of ED symptoms was observed. Further studies should test approaches that target both the management of ED symptoms and the high BMI. Level I, randomized controlled trial TRIAL REGISTRATION: US National Institutes of Health clinical trial registration number NCT02464345, date of registration 1 June 2015.
Publisher: Springer Science and Business Media LLC
Date: 11-05-2021
DOI: 10.1038/S41366-021-00839-W
Abstract: A systematic review with meta-analysis was conducted to synthesise evidence on the efficacy of dietary supplements containing isolated organic compounds for weight loss. Four electronic databases (Medline, Embase, Web of Science, Cinahl) were searched until December 2019. Sixty-seven randomised placebo-controlled trials of dietary supplements containing isolated organic compounds for weight loss were included. Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid and fructans, comparing mean weight difference post-intervention between participants receiving the dietary supplement or placebo. Statistically significant weight differences compared to placebo were observed for chitosan (-1.84 kg 95% confidence interval [CI] -2.79, -0.88 p < 0.01), glucomannan (-1.27 kg 95%CI -2.45, -0.09 p = 0.04), and conjugated linoleic acid (-1.08 kg 95%CI -1.61, -0.55 p < 0.01). None met our threshold for clinical significance (≥2.5 kg). There was no statistically significant effect on weight for fructans compared to placebo (p = 0.24). For dietary supplements with an inadequate number of trials for meta-analysis, a statistically and borderline clinically significant weight difference compared to placebo was found for modified cellulose, manno-oligosaccharides (in males), blood orange juice extract, and three multiple-ingredient dietary supplements. These were only reported in one trial of each. Thus, more evidence is needed before recommending them for weight loss. While some dietary supplements containing isolated organic compounds warrant further investigation to determine efficacy and safety, there is currently insufficient evidence to recommend any of these dietary supplements for weight loss.
Publisher: Informa UK Limited
Date: 08-2003
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.NPEP.2016.10.006
Abstract: Germline deletion of the Prader-Willi syndrome (PWS) candidate gene Snord116 in mice leads to some classical symptoms of human PWS, notably reductions in body weight, linear growth and bone mass. However, Snord116 deficient mice (Snord116
Publisher: Elsevier BV
Date: 03-2010
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/834865
Abstract: Objective . The purpose of this study was to assess the effect of high intensity interval training (HIIT) versus continuous aerobic exercise training (CONT) or placebo (PLA) on body composition by randomized controlled design. Methods . Work capacity and body composition (dual-energy X-ray absorptiometry) were measured before and after 12 weeks of intervention in 38 previously inactive overweight adults. Results . There was a significant group × time interaction for change in work capacity ( P 0 . 001 ), which increased significantly in CONT ( 23.8 ± 3.0 %) and HIIT ( 22.3 ± 3.5 %) but not PLA ( 3.1 ± 5.0 %). There was a near-significant main effect for percentage trunk fat, with trunk fat reducing in CONT by 3.1 ± 1.6 % and in PLA by 1.1 ± 0.4 %, but not in HIIT (increase of 0.7 ± 1.0 %) ( P = 0 . 07 ). There was a significant reduction in android fat percentage in CONT ( 2.7 ± 1.3 %) and PLA ( 1.4 ± 0.8 %) but not HIIT (increase of 0.8 ± 0.7 %) ( P = 0 . 04 ). Conclusion . These data suggest that HIIT may be advocated as a time-efficient strategy for eliciting comparable fitness benefits to traditional continuous exercise in inactive, overweight adults. However, in this population HIIT does not confer the same benefit to body fat levels as continuous exercise training.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2017
Publisher: The Endocrine Society
Date: 07-1999
Abstract: It has been reported that hyperphagia and excessive body weight gain of genetically obese rodents were abolished by adrenalectomy. High hypothalamic levels of neuropeptide Y (NPY) were found in obese rodents. A chronic intracerebroventricular (icv) infusion of NPY in normal rats was shown to produce most hormono-metabolic abnormalities of genetically obese animals, and to be inefficient in doing so in adrenalectomized (ADX) rats. The combined presence of NPY and of glucocorticoids thus appeared to be necessary for inducing obesity. This study, therefore, was aimed at determining the consequences of a chronic i.c.v. NPY infusion in ADX rats receiving or not i.c.v. glucocorticoids. It was found that the combined i.c.v. infusion of NPY and dexamethasone in ADX rats increased food intake, body weight, plasma insulin, leptin, and triglyceride levels relative to vehicle-infused ADX controls. The infusion of NPY alone, or of dexamethasone alone in ADX rats failed to produce these effects. In contrast, the icv infusion of NPY alone greatly decreased the expression of brown adipose tissue uncoupling protein-1 and -3. This was not modified by the superimposed infusion of dexamethasone. It is concluded that, although many of centrally elicited NPY effects require the central presence of glucocorticoids, those bearing on the inhibition of uncoupling proteins expression (energy dissipation) do not require central glucocorticoids.
Publisher: Wiley
Date: 23-02-2009
Publisher: Wiley
Date: 05-01-2023
DOI: 10.1002/ACR.25021
Abstract: To define the association between change in body mass index (BMI) and the risk of knee and hip replacement. We used data from 3 independent cohort studies: the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study, which collected data from adults (45–79 years of age) with or at risk of clinically significant knee osteoarthritis. We conducted Cox proportional hazards regression analysis with clustering of both knees and hips per person to determine the association between change in BMI (our exposure of interest) and the incidence of primary knee and hip replacement over 7–10 years’ follow‐up. Change in BMI (in kg/m 2 ) was calculated between baseline and the last follow‐up visit before knee or hip replacement, or for knees and hips that were not replaced, the last follow‐up visit. A total of 16,362 knees from 8,181 participants, and 16,406 hips from 8,203 participants, were eligible for inclusion in our knee and hip analyses, respectively. Change in BMI was positively associated with the risk of knee replacement (adjusted hazard ratio [HR adj ] 1.03 [95% confidence interval (95% CI) 1.00–1.06]) but not hip replacement (HR adj 1.00 [95% CI 0.95–1.04]). The association between change in BMI and knee replacement was independent of participants’ BMI category at baseline (i.e., normal, overweight, or obese). Public health strategies incorporating weight loss interventions could reduce the burden of knee but not hip replacement surgery.
Publisher: Wiley
Date: 31-08-2012
Publisher: Springer Science and Business Media LLC
Date: 12-2015
DOI: 10.1038/IJO.2015.242
Abstract: Anorexia-cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger. This cytokine acts on feeding centres in the hypothalamus and brainstem to cause anorexia leading to loss of lean and fat mass and eventually cachexia. In animal studies, the circulating concentrations of MIC-1/GDF15 required to cause this syndrome are similar to those seen in patients with advanced cancer, and at least some epidemiological studies support an association between MIC-1/GDF15 serum levels and measures of nutrition. This article will discuss its mechanisms of central appetite regulation, and the available data linking this action to anorexia-cachexia syndromes that suggest it is a potential target for therapy of cancer anorexia-cachexia and conversely may also be useful for the treatment of severe obesity.
Publisher: Elsevier BV
Date: 03-2008
Publisher: Rockefeller University Press
Date: 05-12-2005
DOI: 10.1084/JEM.20051971
Abstract: Psychological conditions, including stress, compromise immune defenses. Although this concept is not novel, the molecular mechanism behind it remains unclear. Neuropeptide Y (NPY) in the central nervous system is a major regulator of numerous physiological functions, including stress. Postganglionic sympathetic nerves innervating lymphoid organs release NPY, which together with other peptides activate five Y receptors (Y1, Y2, Y4, Y5, and y6). Using Y1-deficient (Y1−/−) mice, we showed that Y1−/− T cells are hyperresponsive to activation and trigger severe colitis after transfer into lymphopenic mice. Thus, signaling through Y1 receptor on T cells inhibits T cell activation and controls the magnitude of T cell responses. Paradoxically, Y1−/− mice were resistant to T helper type 1 (Th1) cell–mediated inflammatory responses and showed reduced levels of the Th1 cell–promoting cytokine interleukin 12 and reduced interferon γ production. This defect was due to functionally impaired antigen-presenting cells (APCs), and consequently, Y1−/− mice had reduced numbers of effector T cells. These results demonstrate a fundamental bimodal role for the Y1 receptor in the immune system, serving as a strong negative regulator on T cells as well as a key activator of APC function. Our findings uncover a sophisticated molecular mechanism regulating immune cell functions that can lead to stress-induced immunosuppression.
Publisher: American Physiological Society
Date: 12-2010
DOI: 10.1152/AJPREGU.00345.2010
Abstract: Neuropeptide Y receptors are critical regulators of energy homeostasis and are well known for their powerful influence on feeding, but their roles in other important aspects of energy homeostasis, such as energy expenditure and their functional interactions in these processes, are largely unknown. Here we show that mice lacking both Y2 and Y4 receptors exhibited a reduction in adiposity, more prominent in intra-abdominal vs. subcutaneous fat, and an increase in lean mass as determined by dual-energy X-ray absorptiometry. These changes were more pronounced than those seen in mice with Y2 or Y4 receptor single deletion, demonstrating the important roles and synergy of Y2 and Y4 signaling in the regulation of body composition. These changes in body composition occurred without significant changes in food intake, but energy expenditure and physical activity were significantly increased in Y4 −/− and particularly in Y2 −/− Y4 −/− but not in Y2 −/− mice, suggesting a critical role of Y4 signaling and synergistic interactions with Y2 signaling in the regulation of energy expenditure and physical activity. Y2 −/− and Y4 −/− mice also exhibited a decrease in respiratory exchange ratio with no further synergistic decrease in Y2 −/− Y4 −/− mice, suggesting that Y2 and Y4 signaling each play important and independent roles in the regulation of substrate utilization. The synergy between Y2 and Y4 signaling in regulating fat mass may be related to differences in mitochondrial oxidative capacity, since Y2 −/− Y4 −/− but not Y2 −/− or Y4 −/− mice showed significant increases in muscle protein levels of peroxisome proliferator-activated receptor (PPAR)γ coactivator (PGC)-1α, and mitochondrial respiratory chain complexes I and III. Taken together, this work demonstrates the critical roles of Y2 and Y4 receptors in the regulation of body composition and energy metabolism, highlighting dual antagonism of Y2 and Y4 receptors as a potentially effective anti-obesity treatment.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1093/AJCN/NQAC024
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.COGPSYCH.2018.04.002
Abstract: A robust finding in recognition memory is that performance declines monotonically across test trials. Despite the prevalence of this decline, there is a lack of consensus on the mechanism responsible. Three hypotheses have been put forward: (1) interference is caused by learning of test items (2) the test items cause a shift in the context representation used to cue memory and (3) participants change their speed-accuracy thresholds through the course of testing. We implemented all three possibilities in a combined model of recognition memory and decision making, which inherits the memory retrieval elements of the Osth and Dennis (2015) model and uses the diffusion decision model (DDM: Ratcliff, 1978) to generate choice and response times. We applied the model to four datasets that represent three challenges, the findings that: (1) the number of test items plays a larger role in determining performance than the number of studied items, (2) performance decreases less for strong items than weak items in pure lists but not in mixed lists, and (3) lexical decision trials interspersed between recognition test trials do not increase the rate at which performance declines. Analysis of the model's parameter estimates suggests that item interference plays a weak role in explaining the effects of recognition testing, while context drift plays a very large role. These results are consistent with prior work showing a weak role for item noise in recognition memory and that retrieval is a strong cause of context change in episodic memory.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.CMET.2018.07.018
Abstract: MIC-1/GDF15 is a stress response cytokine and a distant member of the transforming growth factor beta (TGFb) superfamily, with no close relatives. It acts via a recently identified receptor called glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL), which is a distant orphan member of the GDNF receptor family that signals through the tyrosine kinase receptor Ret. MIC-1/GDF15 expression and serum levels rise in response to many stimuli that initiate cell stress and as part of a wide variety of disease processes, most prominently cancer and cardiovascular disease. The best documented actions of MIC-1/GDF15 are on regulation of energy homeostasis. When MIC-1/GDF15 serum levels are substantially elevated in diseases like cancer, it subverts a physiological pathway of appetite regulation to induce an anorexia/cachexia syndrome initiated by its actions on hindbrain neurons. These effects make it a potential target for the treatment of both obesity and anorexia/cachexia syndromes, disorders lacking any highly effective, readily accessible therapies.
Publisher: American Diabetes Association
Date: 04-1997
Abstract: The product of the ob gene, leptin, is a hormone secreted by adipose tissue that acts in the hypothalamus to regulate the size of the body fat depot. Its central administration has been shown to decrease food intake and body weight, while favoring energy dissipation. As glucocorticoids are known to play a permissive role in the establishment and maintenance of obesity syndromes in rodents, it was hypothesized that they do so by restraining the effect of leptin. Leptin injected intracerebroventricularly as a bolus of 3 μg in normal rats induced modest reductions in body weight and food intake. In marked contrast, the same dose of leptin had very potent and long-lasting effects in decreasing both body weight and food intake when administered to adrenalectomized rats. Further, glucocorticoid supplementation of adrenalectomized rats dose-dependently inhibited these potent effects of leptin. These data suggest that glucocorticoids play a key inhibitory role in the action of leptin. Under normal conditions, this inhibitory influence of glucocorticoids may prevent lasting hypophagia. In obesity with degrees of hypercorticism, it may contribute to “leptin resistance,” whose etiology is still little understood.
Publisher: Public Library of Science (PLoS)
Date: 17-06-2021
DOI: 10.1371/JOURNAL.PONE.0253127
Abstract: Meal replacement Severely Energy-Restricted Diets (SERDs) produce ≥ 10% loss of body mass when followed for 6 weeks or longer in people with class III obesity (BMI ≥ 40 kg/m 2 ). The efficacy of SERDs continues to be questioned by healthcare professionals, with concerns about poor dietary adherence. This study explored facilitators and barriers to dietary adherence and program attrition among people with class III obesity who had attempted or completed a SERD in a specialised weight loss clinic. Participants who commenced a SERD between January 2016 to May 2018 were invited to participate. Semi-structured in-depth interviews were conducted from September to October 2018 with 20 participants (12 women and 8 men). Weight change and recounted events were validated using the participants’ medical records. Data were analysed by thematic analysis using line-by-line inductive coding. The mean age ± SD of participants was 51.2 ± 11.3 years, with mean ± SD BMI at baseline 63.7 ± 12.6 kg/m 2 . Five themes emerged from participants’ recounts that were perceived to facilitate dietary adherence: (1.1) SERD program group counselling and psychoeducation sessions, (1.2) emotionally supportive clinical staff and social networks that accommodated and ch ioned change in dietary behaviours, (1.3) awareness of eating behaviours and the relationship between these and progression of disease, (1.4) a resilient mindset, and (1.5) dietary simplicity, planning and self-monitoring. There were five themes on factors perceived to be barriers to adherence, namely: (2.1) product unpalatability, (2.2) unrealistic weight loss expectations, (2.3) poor program accessibility, (2.4) unforeseeable circumstances and (2.5) externalised weight-related stigma. This study highlights opportunities where SERD programs can be optimised to facilitate dietary adherence and reduce barriers, thus potentially improving weight loss outcomes with such programs. Prior to the commencement of a SERD program, healthcare professionals facilitating such programs could benefit from reviewing participants to identify common barriers. This includes identifying the presence of product palatability issues, unrealistic weight loss expectations, socio-economic disadvantage, and behaviour impacting experiences of externalised weight-related stigma.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-12-2020
DOI: 10.1097/GME.0000000000001684
Abstract: Weight loss may be difficult for young women with obesity to achieve due to competing priorities (caring for children and/or full-time work), limiting their ability to engage in weight loss interventions. Older or postmenopausal women may also face challenges to weight loss such as caring responsibilities and menopause. Menopausal status may reflect differences in weight loss. This study compared changes in weight, fat mass, and lean mass in premenopausal versus postmenopausal women in dietary weight loss trials. We reviewed publications from January 2000 to June 2020 evaluating a weight loss intervention with a dietary component, with or without exercise, and reporting weight loss of premenopausal and postmenopausal women. Where available, data on mean change from baseline for weight, fat mass, and lean mass of premenopausal and postmenopausal groups were entered into Review Manger for meta-analyses. Differences between menopausal groups were compared in subgroups of studies for intervention characteristics (diet-only vs diet and exercise dietary modification vs meal replacement 24 wks vs ≥24 wks duration). Seven publications (10 interventions, n = 791) were included three single-arm trials, two randomized controlled trials, and two comparative effectiveness trials. In meta-analyses, there were no statistically significant differences between premenopausal and postmenopausal women (shown as premenopausal minus postmenopausal) for change in weight (0.58 [95% confidence interval −0.12 to 1.28] kg, n = 7 interventions), fat mass (0.73 [−0.25 to 1.70] kg, n = 6 interventions), or lean mass (−0.5 6[−1.48 to 0.36] kg, n = 4 interventions). However, a statistically significant subgroup difference was observed for fat mass change between menopausal groups (premenopausal minus postmenopausal) when comparing diet-only (1.28 [0.23 to 2.33] kg, n = 4 interventions) versus diet and exercise interventions (−0.09 [−0.51 to 0.32]kg, n = 2 interventions). No differences were shown in any other subgroups. This review provides some evidence to suggest weight loss interventions may not need to be tailored to women's menopausal status. However, given the small number of studies, short intervention duration in most publications (≤ 6 mo) and unclear retention rates in premenopausal versus postmenopausal groups of some publications, menopausal group differences should be examined in existing and future trials where the appropriate data have been collected.
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1093/AJCN/NQY048
Abstract: Some country guidelines recommend that people with type 2 diabetes (T2D) limit their consumption of eggs and cholesterol. Our previously published 3-mo weight-maintenance study showed that a high-egg (≥12 eggs/wk) diet compared with a low-egg diet (<2 eggs/wk) did not have adverse effects on cardiometabolic risk factors in adults with T2D. The current study follows the previously published 3-mo weight-maintenance study and assessed the effects of the high-egg compared with the low-egg diets as part of a 3-mo weight-loss period, followed by a 6-mo follow-up period for a total duration of 12 mo. Participants with prediabetes or T2D (n = 128) were prescribed a 3-mo daily energy restriction of 2.1 MJ and a macronutrient-matched diet and instructed on specific types and quantities of foods to be consumed, with an emphasis on replacing saturated fats with monounsaturated and polyunsaturated fats. Participants were followed up at the 9- and 12-mo visits. From 3 to 12 mo, the weight loss was similar (high-egg compared with low-egg diets: -3.1 ± 6.3 compared with -3.1 ± 5.2 kg P = 0.48). There were no differences between groups in glycemia (plasma glucose, glycated hemoglobin, 1,5-anhydroglucitol), traditional serum lipids, markers of inflammation (high-sensitivity C-reactive protein, interleukin 6, soluble E-selectin), oxidative stress (F2-isoprostanes), or adiponectin from 3 to 12 mo or from 0 to 12 mo. People with prediabetes or T2D who consumed a 3-mo high-egg weight-loss diet with a 6-mo follow-up exhibited no adverse changes in cardiometabolic markers compared with those who consumed a low-egg weight-loss diet. A healthy diet based on population guidelines and including more eggs than currently recommended by some countries may be safely consumed. This trial is registered at www.anzctr.org.au/ as ACTRN12612001266853.
Publisher: Springer Science and Business Media LLC
Date: 21-04-2006
DOI: 10.1007/S00125-006-0237-0
Abstract: Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis. Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet. Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy (-/-) mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo-pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity. PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding.
Publisher: Public Library of Science (PLoS)
Date: 28-02-2013
Publisher: Wiley
Date: 15-02-2020
DOI: 10.1111/DOM.13973
Abstract: To update the available evidence on the efficacy and safety of complementary medicines to assist in weight loss by conducting a systematic review and meta-analysis of herbal medicines for weight loss. Four electronic databases (Medline, Embase, CINAHL and Web of Science) were searched from inception until August 2018. A total of 54 randomized placebo-controlled trials of healthy overweight or obese adults were identified. Meta-analyses were conducted for herbal medicines with ≥4 studies available. Weight differences of ≥2.5 kg were considered clinically significant. As a single agent, only Phaseolus vulgaris resulted in a statistically significant weight loss compared to placebo, although this was not considered clinically significant. No effect was seen for Camellia sinensis or Garcinia cambogia. Statistically, but not clinically, significant differences were observed for combination preparations containing C. sinensis, P. vulgaris or Ephedra sinica. Of the herbal medicines trialled in ≤3 randomized controlled trials, statistically and clinically significant weight loss compared to placebo was reported for Irvingia gabonensis, Cissus quadrangularis, and Sphaeranthus indicus combined with Garcinia mangostana, among others, but these findings should be interpreted cautiously because of the small number of studies, generally poor methodological quality, and poor reporting of the herbal medicine interventions. Most herbal medicines appeared safe for consumption over the short duration of the studies (commonly ≤12 weeks). Some warrant further investigation to determine effect size, dosage and long-term safety. There is currently insufficient evidence to recommend any of the herbal medicines for weight loss included in the present review.
Publisher: Wiley
Date: 30-01-2023
DOI: 10.1002/ART.42307
Abstract: To define the association between change in body mass index (BMI) and the incidence and progression of the structural defects of knee osteoarthritis as assessed by radiography. Radiographic analyses of knees at baseline and at 4–5 years of follow‐up were obtained from the following 3 independent cohort studies: the Osteoarthritis Initiative (OAI) study, the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study. Logistic regression analyses using generalized estimating equations, with clustering of both knees within in iduals, were used to investigate the association between change in BMI from baseline to 4–5 years of follow‐up and the incidence and progression of knee osteoarthritis. A total of 9,683 knees (from 5,774 participants) in an “incidence cohort” and 6,075 knees (from 3,988 participants) in a “progression cohort” were investigated. Change in BMI was positively associated with both the incidence and progression of the structural defects of knee osteoarthritis. The adjusted odds ratio (OR) for osteoarthritis incidence was 1.05 (95% confidence interval [95% CI] 1.02–1.09), and the adjusted OR for osteoarthritis progression was 1.05 (95% CI 1.01–1.09). Change in BMI was also positively associated with degeneration (i.e., narrowing) of the joint space and with degeneration of the femoral and tibial surfaces (as indicated by osteophytes) on the medial but not on the lateral side of the knee. A decrease in BMI was independently associated with lower odds of incidence and progression of the structural defects of knee osteoarthritis and could be a component in preventing the onset or worsening of knee osteoarthritis.
Publisher: Springer Science and Business Media LLC
Date: 22-12-2010
Publisher: Public Library of Science (PLoS)
Date: 29-06-2010
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.NPEP.2012.08.010
Abstract: Chronic opiate usage, whether prescribed or illicit, has been associated with changes in bone mass and is a recognized risk factor for the development of osteoporosis however, the mechanism behind this effect is unknown. Here we show that lack of dynorphin, an endogenous opioid, in mice (Dyn-/-), resulted in a significantly elevated cancellous bone volume associated with greater mineral apposition rate and increased resorption indices. A similar anabolic phenotype was evident in bone of mice lacking dynorphin's cognate receptor, the kappa opioid receptor. Lack of opioid receptor expression in primary osteoblastic cultures and no change in bone cell function after dynorphin agonist treatment in vitro indicates an indirect mode of action. Consistent with a hypothalamic action, central dynorphin signaling induces extracellular signal-regulated kinase (ERK) phosphorylation and c-fos activation of neurons in the arcuate nucleus of the hypothalamus (Arc). Importantly, this signaling also leads to an increase in Arc NPY mRNA expression, a change known to decrease bone formation. Further implicating NPY in the skeletal effects of dynorphin, Dyn-/-/NPY-/- double mutant mice showed comparable increases in bone formation to single mutant mice, suggesting that dynorphin acts upstream of NPY signaling to control bone formation. Thus the dynorphin system, acting via NPY, may represent a pathway by which higher processes including stress, reward/addiction and depression influence skeletal metabolism. Moreover, understanding of these unique interactions may enable modulation of the adverse effects of exogenous opioid treatment without directly affecting analgesic responses.
Publisher: Wiley
Date: 14-02-2023
DOI: 10.1002/ACR.25057
Abstract: To define the association between change in body mass index (BMI) and the incidence and progression of structural defects of hip osteoarthritis as assessed by radiography. We used data from 2 independent cohort studies: the Osteoarthritis Initiative (OAI) and the Cohort Hip and Cohort Knee (CHECK) study. Our exposure was change in BMI from baseline to 4–5 years’ follow‐up. Our outcomes were the incidence and progression of structural defects of hip osteoarthritis as assessed using a modified Croft grade in OAI and the Kellgren/Lawrence grade in the CHECK study. To study incidence, we created incidence cohorts of hips without definite overall structural defects at baseline (i.e., grade ) and then investigated the odds of hips having definite overall structural defects at follow‐up (i.e., grade ≥2). To study progression, we created progression cohorts of hips with definite overall structural defects at baseline (i.e., grade ≥2) and then investigated the odds of having a grade increase of ≥1 from baseline to follow‐up. There was a total of 5,896 and 1,377 hips in the incidence cohorts, and 303 and 129 hips in the progression cohorts for the OAI and CHECK study, respectively. Change in BMI (decrease or increase) was not associated with any change in odds of the incidence or progression of definite structural defects of hip osteoarthritis in either the OAI or CHECK cohorts. Weight loss may not be an effective strategy for preventing, slowing, or delaying the structural defects of hip osteoarthritis over 4–5 years.
Publisher: Elsevier BV
Date: 05-2011
Publisher: Elsevier BV
Date: 05-2011
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.NPEP.2011.06.001
Abstract: Prader-Willi syndrome (PWS) is a leading genetic cause of obesity, characterized by hyperphagia, endocrine and developmental disorders. It is suggested that the intense hyperphagia could stem, in part, from impaired gut hormone signaling. Previous studies produced conflicting results, being confounded by differences in body composition between PWS and control subjects. Fasting and postprandial gut hormone responses were investigated in a cross-sectional cohort study including 10 adult PWS, 12 obese subjects matched for percentage body fat and central abdominal fat, and 10 healthy normal weight subjects. PYY[total], PYY[3-36], GLP-1[active] and ghrelin[total] were measured by ELISA or radioimmunoassay. Body composition was assessed by dual energy X-ray absorptiometry. Visual analog scales were used to assess hunger and satiety. In contrast to lean subjects (p<0.05), PWS and obese subjects were similarly insulin resistant and had similar insulin levels. Ghrelin[total] levels were significantly higher in PWS compared to obese subjects before and during the meal (p<0.05). PYY[3-36] meal responses were higher in PWS than in lean subjects (p=0.01), but not significantly different to obese (p=0.08), with an additional non-significant trend in PYY[total] levels. There were no significant differences in self-reported satiety between groups, however PWS subjects reported more hunger throughout (p=0.003), and exhibited a markedly reduced meal-induced suppression of hunger (p=0.01) compared to lean or obese subjects. Compared to adiposity-matched control subjects, hyperphagia in PWS is not related to a lower postprandial GLP-1 or PYY response. Elevated ghrelin levels in PWS are consistent with increased hunger and are unrelated to insulin levels.
Publisher: Wiley
Date: 11-08-2017
DOI: 10.1111/COB.12208
Abstract: The prevalence of depression in those with obesity is reported to be as high as double that in in iduals of normal weight. There is potentially a bi-directional relationship between obesity and depression. Some research has suggested that depression results in weight gain and obesity, and other studies have suggested that those with obesity are more likely to develop depression at a later stage. The aim of this study was to investigate the association of depression symptoms with weight change over a 12-month study. Seventy participants undertook a 3-month lifestyle (diet and exercise) weight loss intervention, and were followed up as part of a 12-month study. Participants completed the Beck Depression Inventory-II (BDI-II) and had their body weight measured throughout the study. Baseline body mass index (BMI) of participants (mean ± standard deviation [SD]) was 31.1 ± 3.9 kg m
Publisher: Wiley
Date: 18-09-2016
DOI: 10.1111/HEPR.12781
Abstract: Regular aerobic exercise reduces visceral adipose tissue (VAT) and liver fat, however, not all in iduals are able to adopt and adhere to such programs. Progressive resistance training (PRT) may be an alternative therapy, but there is limited available evidence. We examined the efficacy of PRT as per current exercise guidelines, compared with sham exercise placebo on liver fat and VAT. Twenty-nine inactive and overweight/obese (body mass index ≥25 kg/m There were no significant group by time interactions for change in liver fat in PRT versus CON groups (-0.07 ± 0.31% vs. 0.55 ± 0.77%, respectively, P = 0.19), VAT (-175 ± 85 cm Traditional PRT is not effective for reducing liver fat in overweight/obese adults compared with placebo control. Although PRT has known metabolic benefits, an adequate volume of aerobic exercise should be promoted if liver fat is the therapeutic target.
Publisher: Wiley
Date: 05-01-2023
DOI: 10.1002/OSP4.654
Abstract: Very low energy diets (VLEDs) effectively induce substantial weight loss in people with obesity, yet they are rarely used as a first line treatment. There is a belief that such diets do not teach the lifestyle behavior changes needed for long‐term weight maintenance. However, little is known about the lived experiences of people who have lost weight on a VLED in the long term. This study aimed to explore the behaviors and experiences of postmenopausal women who had followed a 4‐month VLED (using total meal replacement products [MRPs]), followed by a food‐based, moderately energy‐restricted diet for an additional 8 months, as part of the TEMPO Diet Trial. Qualitative in‐depth semi‐structured interviews were conducted with 15 participants at 12 or 24 months (i.e., at 8 or 20 months post diet completion). Transcribed interviews were analyzed thematically using an inductive approach. Undertaking a VLED was reported by participants to confer advantages in weight maintenance that previous weight loss attempts had not been able to do for them. Firstly, the rapid and significant weight loss, in conjunction with ease of use, was motivational and helped instill confidence in the participants. Secondly, the cessation of a normal diet during the VLED was reported by participants to break weight gain‐inducing habits, allowing them to abandon unhelpful habits and to introduce in their place more appropriate attitudes toward weight maintenance. Lastly, the new identity, helpful habits and increased self‐efficacy around weight loss supported participants during weight maintenance. Additionally, participants reported that ongoing occasional use of MRPs provided a useful and easy new strategy for countering weight regain and supporting their weight maintenance regimen. Among the participants in this qualitative study, most of whom had maintained a loss of over 10% of their baseline body weight at the time of interview, using a VLED in the context of a clinical weight loss trial conferred confidence, motivation and skills for weight maintenance. These findings indicate that VLEDs with clinical support could be successfully leveraged to set up behaviors that will support weight maintenance in the long term.
Publisher: Springer Science and Business Media LLC
Date: 29-12-2022
Publisher: MDPI AG
Date: 20-07-2018
DOI: 10.3390/HEALTHCARE6030085
Abstract: Very low energy diets (VLEDs), commonly achieved by replacing all food with meal replacement products and which result in fast weight loss, are the most effective dietary obesity treatment available. VLEDs are also cheaper to administer than conventional, food-based diets, which result in slow weight loss. Despite being effective and affordable, these diets are underutilized by healthcare professionals, possibly due to concerns about potential adverse effects on body composition and eating disorder behaviors. This paper describes the rationale and detailed protocol for the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity), in a randomized controlled trial comparing the long-term (3-year) effects of fast versus slow weight loss. One hundred and one post-menopausal women aged 45–65 years with a body mass index of 30–40 kg/m2 were randomized to either: (1) 16 weeks of fast weight loss, achieved by a total meal replacement diet, followed by slow weight loss (as for the SLOW intervention) for the remaining time up until 52 weeks (“FAST” intervention), or (2) 52 weeks of slow weight loss, achieved by a conventional, food-based diet (“SLOW” intervention). Parameters of body composition, cardiometabolic health, eating disorder behaviors and psychology, and adaptive responses to energy restriction were measured throughout the 3-year trial.
Publisher: Wiley
Date: 23-08-2022
DOI: 10.1111/OBR.13465
Abstract: This systematic review with meta‐analyses assessed the effects of total diet replacement (TDR) programs on mental well‐being in clinical trial participants with a body mass index greater than or equal to 25 kg/m 2 . TDR programs involve replacing all dietary requirements with nutritionally replete formula foods and are generally administered to induce rapid weight loss. To date, it is largely unclear what effects TDR programs may have on mental well‐being, particularly in the long‐term. To address this, we screened 25,976 references across six databases and extracted 35 publications. These 35 publications provided sufficient data to evaluate the effects of TDR programs on depression, anxiety, stress, positive affect, negative affect, vitality, role‐emotional, social functioning, mental health, mental composite summary score, self‐esteem, and general psychological health in 24 meta‐analyses. Due to the lack of research comparing TDR programs to comparator groups, 22 of our 24 meta‐analyses explored change in these mental well‐being sub‐domains over time in TDR programs without comparators. Specifically, we assessed the change from pre‐diet (before the TDR program) to either post‐diet (up to and including two months after the TDR program) and/or follow‐up (more than two months after the TDR program). For depression and anxiety, we were also able to assess the change from pre‐diet to mid‐diet (which fell within two weeks of the diet half‐way point). The remaining two meta‐analyses assessed the difference in depression scores between a TDR group and a food‐based comparator group from pre‐diet to post‐diet and from pre‐diet to follow‐up. Across all meta‐analyses, our results found no marked adverse effects of TDR programs on any mental well‐being sub‐domain. In fact, clear improvements were observed for depression, anxiety, stress, vitality, role‐emotional, and social functioning at post‐diet. Interestingly, the improvements for depression, vitality and role‐emotional were maintained at follow‐up. All improvements were observed in meta‐analyses without comparators. While the two comparator‐based meta‐analyses showed no difference between TDR programs and food‐based diets in depression symptoms, there was low statistical power. For all meta‐analyses containing three or more independent s les, we constructed prediction intervals to determine the range within which the mean of the true effects may fall for future populations. While these prediction intervals varied between sub‐domains, we found that mean depression scores are only likely to increase (i.e., depression will worsen) in less than 3% of future TDR interventions which meet our inclusion/exclusion criteria. Taken together, we concluded that for adults with a body mass index greater than or equal to 25 kg/m 2 , TDR programs are unlikely to lead to marked adverse effects on mental well‐being. These findings do not support the exclusion of participants from trials or interventions involving TDR programs based on concerns that these programs may adversely affect mental well‐being. In fact, by excluding these participants, they may be prevented from improving their metabolic health and mental well‐being.
Publisher: MDPI AG
Date: 20-02-2018
DOI: 10.3390/NU10020239
Publisher: The Endocrine Society
Date: 31-05-2018
Abstract: Pubertal adolescents show strong appetites. How this is mediated is unclear, but ghrelin and peptide YY (PYY) play potentially important roles. To measure ghrelin and PYY change in relation to pubertal growth. Three-year prospective cohort study. Australian regional community. Eighty healthy adolescents (26 girls 54 boys) recruited at 10 to 13 years. Fasting circulating total ghrelin, total PYY, IGF-1, insulin, leptin (via radioimmunoassay), estradiol and testosterone (via mass spectrometry), anthropometry, and body composition (via bioelectrical impedance). Adolescents exhibited normal developmental change. Mixed models revealed positive associations for ghrelin to age2 (both sexes: P & 0.05), indicating a U-shaped trend over time. Ghrelin was also inversely associated with IGF-1 (both sexes: P & 0.05), leptin in girls (P & 0.01), and insulin in boys (P & 0.05) and negatively correlated with annual height and weight velocity (both sexes: P ≤ 0.01). PYY showed no age-related change in either sex. Neither ghrelin nor PYY were associated with Tanner stage. Weight subgroup analyses showed significant ghrelin associations with age2 in healthy-weight but not overweight and obese adolescents (7 girls 18 boys). Adolescents showed a U-shaped change in ghrelin corresponding to physical and biochemical markers of growth, and no change in PYY. The overweight and obesity subgroup exhibited an apparent loss of the U-shaped ghrelin trend, but this finding may be attributed to greater maturity and its clinical significance is unclear. Further research on weight-related ghrelin and PYY trends at puberty is needed to understand how these peptides influence growth and long-term metabolic risk.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2022
DOI: 10.1186/S12888-022-04005-Y
Abstract: Bulimia nervosa (BN) and binge eating disorder (BED) are eating disorders (EDs) characterized by recurrent binge eating. They are associated with medical complications, impaired adaptive function and often a high BMI, for which a multidisciplinary treatment approach may be needed. This study explored the efficacy of a novel intervention integrating Cognitive Behavioural Therapy- Enhanced (CBT-E) and weight management for people with recurrent binge eating episodes and high BMI with respect to physical, psychopathological and quality of life outcomes. Ninety-eight adults diagnosed with BN, BED, or Other Specified/Unspecified Feeding or Eating Disorder (OSFED/UFED) and BMI ≥ 27 to kg/m 2 were randomized to a multidisciplinary approach, the Healthy APproach to weIght management and Food in Eating Disorders (HAPIFED) or to CBT-E. Metabolic parameters, health-related quality of life, general psychological and ED symptoms and ED diagnostic status outcomes are reported. Data were analyzed with mixed effects models adopting multiple imputed datasets where data were missing. Both HAPIFED and CBT-E showed statistical significance for the time effect, with reduction in stress ( p 0.001), improvement in mental health-related quality of life ( p = 0.032), reduction in binge eating severity ( p 0.001), and also in global ED symptoms scores ( p 0.001), with the significant changes found at end of treatment and sustained at 12-month follow-up. However, no statistical significance was found for differences between the interventions in any of the outcomes measured. Despite a high BMI, most participants ( 75%) had blood test results for glucose, insulin, triglycerides and cholesterol within the normal range, and 52% were within the normal range for the physical component of quality of life at baseline with no change during the trial period. Integrating weight and ED management resulted in comparable outcomes to ED therapy alone. Although adding weight management to an ED intervention had no adverse effects on psychological outcomes, it also had no beneficial effect on metabolic outcomes. Therefore, more intense weight management strategies may be required where indicated to improve metabolic outcomes. Safety will need to be concurrently investigated. US National Institutes of Health clinical trial registration number NCT02464345 , date of registration 08/06/2015. Changes to the present paper from the published protocol paper (Trials 18:578, 2015) and as reported in the Trial registration (clinicaltrials.gov) are reported in Supplementary File 1.
Publisher: American Diabetes Association
Date: 15-11-2012
DOI: 10.2337/DB12-0156
Abstract: Recruitment of activated immune cells into white adipose tissue (WAT) is linked to the development of insulin resistance and obesity, but the mechanism behind this is unclear. Here, we demonstrate that Y1 receptor signaling in immune cells controls inflammation and insulin resistance in obesity. Selective deletion of Y1 receptors in the hematopoietic compartment of mice leads to insulin resistance and inflammation in WAT under high fat–fed conditions. This is accompanied by decreased mRNA expression of the anti-inflammatory marker adiponectin in WAT and an increase of the proinflammatory monocyte chemoattractant protein-1 (MCP-1). In vitro, activated Y1-deficient intraperitoneal macrophages display an increased inflammatory response, with exacerbated secretion of MCP-1 and tumor necrosis factor, whereas addition of neuropeptide Y to wild-type macrophages attenuates the release of these cytokines, this effect being blocked by Y1 but not Y2 receptor antagonism. Importantly, treatment of adipocytes with the supernatant of activated Y1-deficient macrophages causes insulin resistance, as demonstrated by decreased insulin-induced phosphorylation of the insulin receptor and Akt as well as decreased expression of insulin receptor substrate 1. Thus, Y1 signaling in hematopoietic-derived cells such as macrophages is critical for the control of inflammation and insulin resistance in obesity.
Publisher: Springer Science and Business Media LLC
Date: 15-05-2021
DOI: 10.1038/S41366-021-00832-3
Abstract: This study aims to investigate the association between weight change and total knee or hip replacement (TKR or THR) for OA among middle-aged and older adults with overweight or obesity. Weight data were collected in 2006–2009 and in 2010 from the 45 and Up Study—a population-based cohort aged ≥45 years in New South Wales, Australia. Participants were included if they had a baseline body mass index (BMI) ≥ 25 kg/m 2 and no history of TKR or THR. Weight change was categorised into four groups: .5% loss –7.5% loss stable (≤5% change) and % gain. Hospital admission data were linked to identify TKR and THR for OA, and multivariable Cox regression was used to assess risk of TKR and THR. Of 23,916 participants, 2139 lost .5% weight, 1655 lost 5–7.5% weight, and 4430 gained % weight. Over 5.2 years, 1009 (4.2%) underwent TKR and 483 (2.0%) THR. Compared to weight-stable, weight loss of .5% was associated with reduced risk of TKR after adjusting for age, sex, BMI, socioeconomic and lifestyle factors (hazard ratio 0.69, 95%CI 0.54–0.87), but had no association with THR. Weight loss of 5–7.5% was not associated with altered risk of either TKR or THR. Weight gain was associated with increased risk of THR after adjusting for confounders, but not TKR. This study suggests that a weight loss target .5% is required to reduce the risk of TKR in adults with overweight or obesity. Weight gain should be avoided as it increases the risk of THR.
Publisher: Springer Science and Business Media LLC
Date: 03-1994
DOI: 10.1007/BF00398049
Publisher: Elsevier BV
Date: 06-2007
Publisher: MDPI AG
Date: 03-09-2015
DOI: 10.3390/NU7095344
Publisher: Elsevier BV
Date: 06-2010
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.BONE.2010.10.174
Abstract: Neuropeptide Y, Y1 receptors are found in neuronal as well as bone tissue and Y1 signalling has been implicated in the regulation of bone mass. However, the contribution of Y1 receptors located in these different tissues, particularly that of the bone-specific Y1 receptors, to the regulation of bone homeostasis is unclear. Here we demonstrate that osteoblast-specific Y1 receptor deletion resulted in a marked increase in femoral cancellous bone volume, trabecular thickness and trabecular number. This is the result of elevated osteoblast activity as shown by increased mineral apposition rate and bone formation rate, and is associated with an upregulation in the mRNA expression levels of alkaline phosphatase, osteocalcin and dentin matrix protein-1. Furthermore, osteoblastic Y1 receptor deletion also led to increased mineral apposition rate on both the endocortical and the periosteal surfaces resulting in increased femoral diameter. Together these data demonstrate a direct role for the Y1 receptor on osteoblasts in the regulation of osteoblast activity and bone formation in vivo and suggest that targeting Y1 receptor signalling directly in the bone may have potential therapeutic implications for stimulating bone accrual in diseases such as osteoporosis.
Publisher: S. Karger AG
Date: 1999
DOI: 10.1159/000015254
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.NPEP.2012.04.001
Abstract: Peptide YY (PYY) is best known for its important role in appetite regulation, but recent pharmacological studies have suggested that PYY is also involved in regulating energy balance and glucose homeostasis. However, the mechanism behind the regulation of these parameters by PYY is less clear. Here, by utilising an inducible transgenic mouse model where PYY overexpression is induced in adult animals (PYYtg) and release of mature PYY peptides is controlled by endogenous machineries, we show that elevating PYY levels leads to reduced food intake after a 24-h fast. Furthermore, PYYtg mice, although not significantly different from WT with respect to body weight, adiposity, lean mass, physical activity or energy expenditure, exhibited a significantly increased respiratory exchange ratio (RER), indicating decreased lipid oxidation and/or increased lipogenesis. Importantly, PYYtg mice showed a 25% reduction in liver protein levels of phosphorylated acetyl-CoA carboxylase (pACC) in the absence of changes in total ACC levels compared to those of WT mice. Moreover, liver protein levels of AMP-activated kinase (AMPK) in PYYtg mice were 25% lower than those of WT mice, consistent with a reduced pACC in these mice. These data suggest that elevation of PYY levels as seen after a meal can increase lipogenic capacity, which is likely a key contributor to the increased RER seen in PYYtg mice. In addition, PYYtg mice exhibited comparable insulin tolerance and oral glucose tolerance to those of WT, but showed a trend towards decreased insulin levels in response to an oral glucose challenge, indicating that PYY could improve insulin action. Taken together, these findings demonstrate that under physiological conditions, PYY reduces food intake while enhancing lipogenic capacity and insulin action, likely contributing to fuel assimilation in the postprandial state.
Publisher: Informa UK Limited
Date: 19-01-2015
DOI: 10.1586/17446651.2015.1001741
Abstract: Obesity is no longer considered to provide protection against osteoporosis. Moreover, treatments for obesity are now suspected of reducing bone mass. With the escalating incidence of obesity, combined with increases in the frequency, duration and intensity of interventions used to combat it, we face a potential increase in health burden due to osteoporotic fractures. The neuropeptide Y-ergic system offers a potential target for the prevention and anabolic treatment of bone loss in obesity, due to its dual role in the regulation of energy homeostasis and bone mass. Although the strongest stimulation of bone mass by this system appears to occur via indirect hypothalamic pathways involving Y2 receptors (one of the five types of receptors for neuropeptide Y), Y1 receptors on osteoblasts (bone-forming cells) induce direct effects to enhance bone mass. This latter pathway may offer a suitable target for anti-osteoporotic treatment while also minimizing the risk of adverse side effects.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2014
Publisher: MDPI AG
Date: 06-07-2018
Publisher: Elsevier BV
Date: 06-2016
Publisher: Wiley
Date: 25-10-2012
Publisher: MDPI
Date: 07-05-2018
Publisher: Wiley
Date: 17-11-2015
DOI: 10.1111/OBR.12230
Abstract: Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. In iduals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and in iduals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although in iduals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.
Publisher: Elsevier BV
Date: 03-2006
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: American Diabetes Association
Date: 12-1995
Abstract: Obesity and non-insulin-dependent diabetes are estimated to affect millions of people in the world. This pathology is multifactorial, comprising complex interactions of genetic and environmental factors and lacking a specific therapy. Great interest arose from the recent discovery of the ob gene expressed only in adipose tissue and coding for a protein that appears to regulate adiposity, potentially by acting as a satiety factor. We report here that in normal rats, ob mRNA is respectively up- or downregulated by a rise in insulinemia (induced by 2-day insulin infusion while maintaining euglycemia) or a decrease in insulinemia (induced by a 3-day fast). Our results also show that in genetically obese fa/fa rats studied longitudinally, white adipose tissue ob mRNA levels increase in parallel with early occurringand steadily increasing hyperinsulinemia. This results in adult obese animals having markedly higher ob mRNA levels than age-matched normoinsulinemic lean rats. Furthermore, in adult obese rats, ob mRNA escapes down-regulation as normalization of hyperinsulinemia due to fasting fails to reduce the high ob mRNA levels.
Publisher: American Medical Association (AMA)
Date: 30-10-2019
Publisher: Wiley
Date: 10-06-2020
DOI: 10.1002/OSP4.432
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.JHEP.2015.02.022
Abstract: Aerobic exercise reduces liver fat and visceral adipose tissue (VAT). However, there is limited data from randomized trials to inform exercise programming recommendations. This study examined the efficacy of commonly prescribed exercise doses for reducing liver fat and VAT using a randomized placebo-controlled design. Inactive and overweight/obese adults received 8 weeks of either i) low to moderate intensity, high volume aerobic exercise (LO:HI, 50% VO 2peak, 60 min, 4d/week) ii) high intensity, low volume aerobic exercise (HI:LO, 70% VO 2peak, 45 min, 3d/week) iii) low to moderate intensity, low volume aerobic exercise (LO:LO, 50% VO 2peak, 45 min, 3d/week) or iv) placebo (PLA). Liver fat (spectroscopy) and VAT (magnetic resonance imaging) were measured before and after intervention. Forty-seven of the 48 (n = 12 in each group) participants completed the trial. There were no serious adverse events. There was a significant change in group × time interaction in liver fat, which reduced in HI:LO by 2.38 ± 0.73%, in LO:HI by 2.62 ± 1.00%, and in LO:LO by 0.84 ± 0.47% but not in PLA (increase of 1.10 ± 0.62%) (p = 0.04). There was a significant reduction in VAT in HI:LO (-258.38 ± 87.78 cm(3)), in LO:HI (-386.80 ± 119.5 cm(3)), and in LO:LO (-212.96 ± 105.54 cm(3)), but not in PLA (92.64 ± 83.46 cm(3)) (p = 0.03). There were no significant differences between the dose or intensity of the exercise regimen and reductions in liver fat or VAT (p > 0.05). The study found no difference in efficacy of liver fat reduction by either aerobic exercise dose or intensity. All of the aerobic exercise regimens employed reduced liver fat and VAT by a small amount without clinically significant weight loss.
Publisher: Springer Science and Business Media LLC
Date: 30-05-2014
Publisher: Wiley
Date: 02-2009
DOI: 10.1359/JBMR.081013
Abstract: Important and novel roles for neuropeptide Y (NPY) signaling in the control of bone homeostasis have recently been identified, with deletion of either the Y1 or Y2 receptors resulting in a generalized increase in bone formation. Whereas the Y2 receptor-mediated anabolic response is mediated by a hypothalamic relay, the Y1-mediated response is likely mediated by osteoblastic Y1 receptors. The presence of Y1 receptors on osteoblasts and various other peripheral tissues suggests that, in addition to neuronal input, circulating factors may also interact with the Y1-mediated pathways. The skeletal and adipose tissue (peripheral and marrow) responses to Y1 receptor deficiency were examined after (1) leptin deficiency, (2) gonadectomy, and (3) hypothalamic NPY overexpression. Bone formation was consistently increased in intact Y1(-/-) mice. However, the hypogonadism of gonadectomy or leptin deficiency blocked this anabolism in male Y1(-/-) mice, whereas females remained unchanged. The Y1-mediated bone anabolic pathway thus seems to be dependent on the presence of intact androgen signaling. Y1 deficiency also led to increased body weight and/or adiposity in all experimental models, with the exception of male ob/ob, showing a general adipogenic effect of Y1 deficiency that is not dependent on androgens. Interestingly, marrow adipocytes were regulated differently than general adipose depots in these models. Taken together, this interaction represents a novel mechanism for the integration of endocrine and neural signals initiated in the hypothalamus and provides further insight into the coordination of bone and energy homeostasis.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.NPEP.2010.01.001
Abstract: Gut-derived peptides are known to regulate food intake by activating specific receptors in the brain, but the target nuclei and neurons influenced are largely unknown. Here we show that peripherally administered pancreatic polypeptide (PP) stimulates neurons in key nuclei of the hypothalamus critical for appetite and satiety regulation. In the lateral hypothalamic area (LHA), also known as the feeding center, neurons expressing the orexigenic neuropeptide orexin co-localize with the early neuronal activation marker c-Fos upon i.p. injection of PP into mice. In the ventromedial hypothalamus (VMH), also known as the satiety center, neurons activated by PP, as indicated by induction of c-Fos immunoreactivity, express the anorexigenic brain-derived neurotrophic factor (BDNF). Activation of neurons in the LHA and VMH in response to PP occurs via a Y4 receptor-dependent process as it is not seen in Y4 receptor knockout mice. We further demonstrate that in response to i.p. PP, orexin mRNA expression in the LHA is down-regulated, with Y4 receptors being critical for this effect as it is not seen in Y4 receptor knockout mice, whereas BDNF mRNA expression is up-regulated in the VMH in response to i.p. PP in the fasted, but not in the non-fasted state. Taken together these data suggest that PP can regulate food intake by suppressing orexigenic pathways by down-regulation of orexin and simultaneously increasing anorexigenic pathways by up-regulating BDNF.
Publisher: Public Library of Science (PLoS)
Date: 22-12-2009
Publisher: Elsevier BV
Date: 03-2023
Publisher: Wiley
Date: 19-04-2023
DOI: 10.1111/JGS.18371
Abstract: Most guidelines recommending weight loss for hip osteoarthritis are based on research on knee osteoarthritis. Prior studies found no association between weight loss and hip osteoarthritis, but no previous studies have targeted older adults. Therefore, we aimed to determine whether there is any clear benefit of weight loss for radiographic hip osteoarthritis in older adults because weight loss is associated with health risks in older adults. We used data from white female participants aged ≥65 years from the Study of Osteoporotic Fractures. Our exposure of interest was weight change from baseline to follow‐up at 8 years. Our outcomes were the development of radiographic hip osteoarthritis (RHOA) and the progression of RHOA over 8 years. Generalized estimating equations (clustering of 2 hips per participant) were used to investigate the association between exposure and outcomes adjusted for major covariates. There was a total of 11,018 hips from 5509 participants. There was no associated benefit of weight loss for either of our outcomes. The odds ratios (95% confidence intervals) for the development and progression of RHOA were 0.99 (0.92–1.07) and 0.97 (0.86–1.09) for each 5% weight loss, respectively. The results were consistent in sensitivity analyses where participants were limited to those who reported trying to lose weight and who also had a body mass index in the overweight or obese range. Our findings suggest no associated benefit of weight loss in older female adults in the structure of the hip joint as assessed by radiography.
Publisher: MDPI AG
Date: 28-02-2017
DOI: 10.3390/BS7010010
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.TEM.2010.02.004
Abstract: The hypothalamus regulates the skeleton and adipose tissue via endocrine mechanisms. Changes in sex steroid levels in menopause and aging are central to the associated changes in bone mass and adiposity. Whereas many of these effects occur via direct actions on osteoblasts or adipocytes, sex hormones can also mediate effects on bone and adipose tissue via interaction with neuronal pathways. A key hypothalamic regulator of bone and adipose tissue is neuropeptide Y (NPY), which coordinately influences these tissues via effects on neuroendocrine and sympathetic nervous output. Better understanding of the interaction between NPY and sex steroids in regulating skeletal and energy homeostasis could lead to more effective treatments for osteoporosis and obesity.
Publisher: The Endocrine Society
Date: 07-2006
DOI: 10.1210/ME.2005-0494
Abstract: Mutations in the human ALMS1 gene are responsible for Alström syndrome, a disorder in which key metabolic and endocrinological features include childhood-onset obesity, metabolic syndrome, and diabetes, as well as infertility. ALMS1 localizes to the basal bodies of cilia and plays a role in intracellular trafficking, but the biological functions of ALMS1 and how these relate to the pathogenesis of obesity, diabetes, and infertility remain unclear. Here we describe a new mouse model of Alström syndrome, fat aussie, caused by a spontaneous mutation in the Alms1 gene. Fat aussie (Alms1 foz/foz) mice are of normal weight when young but, by 120 d of age, they become obese and hyperinsulinemic. Diabetes develops in Alms1 foz/foz mice accompanied by pancreatic islet hyperplasia and islet cysts. Female mice are fertile before the onset of obesity and metabolic syndrome however, male fat aussie mice are sterile due to a progressive germ cell loss followed by an almost complete block of development at the round-to-elongating spermatid stage of spermatogenesis. In conclusion, Alms1 foz/foz mouse is a new animal model in which to study the pathogenesis of the metabolic and fertility defects of Alström syndrome, including the role of ALMS1 in appetite regulation, pathogenesis of the metabolic syndrome, pancreatic islet physiology, and spermatogenesis.
Publisher: The Endocrine Society
Date: 2015
DOI: 10.1210/JC.2014-2646
Abstract: Reference intervals for bone turnover markers (BTMs) and relationships between BTM and fracture risk in older men are not well characterized. The purpose of this article was to determine the reference intervals for serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (PINP), and collagen type I C-terminal cross-linked telopeptide (CTX-I) in healthy older men and to explore factors associated with BTMs, including hip fracture risk. We studied a population-based cohort of 4248 men aged 70 to 89 years, 4008 of whom had serum s les available for analysis. Morning blood s les were collected at the study visit. Comorbid conditions were assessed by questionnaire. The reference s le comprised fasting men (n = 298, median age 75.3 years [interquartile range 73.9-78.1 years) reporting excellent or very good health, without a history of diabetes, cardiovascular disease, cancer, depression, or dementia. Serum tOC, PINP, and CTX-I were estimated by automated electrochemiluminescence immunoassays, ucOC was estimated using hydroxyapatite binding, and incident hip fractures were captured from hospital admission data. Reference intervals for tOC, ucOC, PINP, and CTX-I were 10.2 to 41.0, 5.2 to 21.9, 18 to 129 μg/L, and 117 to 740 ng/L, respectively. tOC, ucOC and CTX-I were associated with hip fracture incidence, but after adjustment for other risk factors only tOC remained significantly associated. Reference intervals for BTMs in older men have been defined. tOC may be more informative for hip fracture risk in older men than CTX-I and PINP. Further studies are needed to clarify the utility of BTM reference intervals in the management of aging men at risk of osteoporosis.
Publisher: Wiley
Date: 05-09-2013
DOI: 10.1002/OBY.20534
Abstract: Peptide YY (PYY3-36) and pancreatic polypeptide (PP) potently inhibit food intake in rodents and humans, however, it is unclear whether they have any synergistic/additive interaction in decreasing food intake. Fasted WT, Y2(-) (/) (-) , Y4(-) (/) (-) , or Y2Y4(-) (/) (-) mice were i.p. administrated with saline, PYY3-36, and/or PP. Combined injection of PYY3-36 and PP reduces food intake in an additive manner was demonstrated in this study. This effect is mediated via Y2 and Y4 receptors, respectively. It was demonstrated that PYY3-36 and PP activate distinct neuronal pathways in the hypothalamus, as demonstrated by immunostaining for c-fos, which shows distinct patterns in response to either hormone. After PYY3-36 injection, neurons in the dorsal aspect of the arcuate nucleus (Arc), paraventricular nucleus, and dorso-medial nucleus of the hypothalamus (DMH) are activated with minimal responses seen in the ventro-medial nucleus of the hypothalamus (VMH) and lateral hypothalamic area (LHA) of WT mice. These effects are absent in Y2(-) (/) (-) mice. PP activates preferably the lateral aspect of the Arc, the DMH, VMH, and LHA in a Y4 receptor-dependent manner. Importantly, the expression pattern of c-fos immunoreactive neurons induced by combined treatment appears to be the sum of the effects of single treatments rather than a result of synergistic interaction. These findings demonstrate that PYY3-36 and PP activate distinct pathways in the hypothalamus to reduce food intake in an additive manner.
Publisher: Wiley
Date: 31-05-2016
DOI: 10.1002/OSP4.48
Publisher: American Society for Clinical Investigation
Date: 07-1993
DOI: 10.1172/JCI116543
Publisher: The Endocrine Society
Date: 07-2010
DOI: 10.1210/JC.2009-2492
Abstract: Background: Subjects with Prader-Willi syndrome (PWS) have a reduced life expectancy due to cardiovascular disease. Increased systemic low-grade inflammation is postulated as a contributor, despite reported lower visceral fat mass and increased insulin sensitivity. Objectives: Our aim was to compare inflammatory markers and arterial stiffness in PWS and adiposity-matched obese control subjects. Design: We conducted a cross-sectional cohort study comparing 12 PWS subjects, 12 obese subjects matched for percentage body fat and central abdominal fat mass, and 10 healthy normal-weight subjects. Main Outcome Measures: Dual-energy x-ray absorptiometry was used to assess body composition, flow cytometry to quantify activation markers on immune cells, and ELISA for measurement of C-reactive protein, adiponectin, and IL-6. Insulin resistance was estimated by homeostasis model assessment and arterial stiffness by applanation tonometry. Results: PWS and obese subjects had similarly increased homeostasis model assessment and arterial stiffness. Nevertheless, PWS subjects showed significantly higher IL-6 (4.9 ± 1.0 vs. 2.5 ± 0.4 pg/ml P = 0.02) and nonsignificantly higher C-reactive protein (10.5 ± 3.2 vs. 4.0 ± 1.0 ng/ml P = 0.08). Neutrophil activation markers CD66b and CD11b were higher in PWS compared to obese subjects (P & 0.01), reflecting an activated innate immune system. These markers were positively related to central adiposity in lean and obese subjects (r = 0.49 P & 0.05), but not in PWS subjects. Conclusions: PWS subjects compared to adiposity-matched obese subjects demonstrate similar insulin resistance but increased low-grade inflammation. The dissociation of inflammation and central adiposity suggests that activation of innate immunity may be either a specific genetic feature of PWS or linked to the commonly associated obstructive sleep apnea syndrome, and might offer a treatment target to reduce cardiovascular disease.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1093/JN/NXAB311
Abstract: Severely energy-restricted diets that utilize meal-replacement products are the most effective dietary treatment for obesity. However, there are concerns they may fail to educate in iduals on how to adopt a healthy food-based diet after weight loss. The aim of this research was to compare changes in diet quality following total meal replacement compared with food-based weight-loss diets. In this secondary analysis of a randomized controlled trial, 79 postmenopausal women aged 45-65 y, with a BMI (in kg/m2) of 30-40, were randomly assigned to either a total meal-replacement diet (energy intake restricted by 65-75% relative to requirements) for 16 wks, followed by a food-based diet (energy intake restricted by 25-35% relative to requirements) until 52 wks, or the food-based diet for the entire 52-wk period. Diet quality was scored at baseline and 52 wks using the Healthy Eating Index for Australian Adults, with score changes compared between groups using an independent t test. Diet quality improved from baseline in both groups, but less so in the total meal-replacement group, with a mean (SD) increase of 3.6 (10.8) points compared with 11.8 (13.9) points in the food-based group, resulting in a mean between-group difference of -8.2 (P = 0.004 95% CI: -13.8, -2.7) points. This improvement in diet quality within both groups was mostly driven by a reduction in the intake of discretionary foods. Intake remained below the recommendations at 52 wks for 4 of the 5 food groups in both dietary interventions. In postmenopausal women with obesity, weight-loss interventions that involve either a total meal-replacement diet or a food-based diet both improve diet quality, however, not sufficiently to meet recommendations. This highlights the importance of addressing diet quality as a part of all dietary weight-loss interventions. This trial is registered with the Australia and New Zealand Clinical Trials Registry as 12612000651886.
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.NPEP.2004.10.002
Abstract: Gene knockout approaches have helped to better understand the functions of the different Y receptors. However, some results obtained from these knockout mice are unexpected and differ from the results of pharmacological intervention experiments. One possible explanation for this is that germ-line gene deletion of a particular Y receptor can influence expression and function of the remaining Y receptors. Here we show that such compensation in mRNA and protein expression does occur in Y receptor single, double and triple knockout models. Radio-ligand binding experiments using [(125)I]-PYY revealed significant up- and down-regulation of remaining Y receptor binding sites in various Y receptor knockout models compared to results from control mice employing Y receptor preferring agonist or antagonists for displacement of the radio-ligand. The most obvious change can be seen in the hippoc us of Y(1) knockout mice, where the level of the remaining Y receptors is strongly down-regulated. In Y(2) knockout mice no such trend can be seen, however, the expression pattern is significantly changed with a strong up-regulation of [(125)I]-PYY specific binding in the dentate gyrus. Interestingly, this pattern was also seen in Y(1)Y(2)Y(4) triple knockout mice. Y(5) receptor mRNA was approximately 20% higher in the hippoc us and dentate gyrus in the triple knockout mice compared to wild-type controls, while Y(6) mRNA expression could not be detected. However, competition binding experiments in Y(1)Y(2)Y(4) triple knockout mice with the Y(5) receptor preferring ligands [Leu(31), Pro(34)] NPY and [A(31), Aib(32)] NPY were able to replace only approximately 50% of [(125)I]-PYY binding in the dentate gyrus suggesting the existence of further yet unidentified Y receptor(s).
Publisher: Proceedings of the National Academy of Sciences
Date: 16-08-2004
Abstract: Neuropeptide Y (NPY) is pivotal in the coordinated regulation of food intake, growth, and reproduction, ensuring that procreation and growth occur only when food is abundant and allowing for energy conservation when food is scant. Although emotional and behavioral responses from the higher brain are known to be involved in all of these functions, understanding of the coordinated regulation of emotion/behavior and physiological functions is lacking. Here, we show that the NPY system plays a central role in this process because ablation of the Y1 receptor gene leads to a strong increase in territorial aggressive behavior. After exposure to the resident-intruder test, expression of c-fos mRNA in Y1-knockout mice is significantly increased in the medial amygdala, consistent with the activation of centers known to be important in regulating aggressive behavior. Expression of the serotonin [5-hydroxytryptamine (5-HT)] synthesis enzyme tryptophan hydroxylase is significantly reduced in Y1-deficient mice. Importantly, treatment with a 5-HT-1A agonist, (±)-8-hydroxy-2-(di- n -propylamino)tetralin hydrobromide, abolished the aggressive behavior in Y1-knockout mice. These results suggest that NPY acting through Y1 receptors regulates the 5-HT system, thereby coordinately linking physiological survival mechanisms such as food intake with enabling territorial aggressive behavior.
Publisher: Elsevier BV
Date: 06-2007
Publisher: Elsevier BV
Date: 06-2020
Publisher: Wiley
Date: 11-06-2015
DOI: 10.1111/OBR.12295
Abstract: Severe dietary energy restriction is often used for overweight or obese in iduals to achieve rapid weight loss and related health improvements. However, the extent of putative adverse effects on eating behaviour is unknown. We thus systematically searched seven databases for studies that assessed binge eating before and after severe dietary energy restriction (low or very low energy diets) in overweight or obese in iduals. Fifteen clinically supervised interventions from 10 publications (nine of which involved only women) were included. Among in iduals with clinically relevant pre-treatment binge eating disorder, severe dietary energy restriction significantly decreased binge eating in all four interventions involving this population, at least during the weight loss programme. In contrast, no consistent association between severe dietary energy restriction and the onset of bingeing was found in 11 interventions involving in iduals without pre-treatment binge eating disorder, with four such interventions showing significant increases, two showing no change, and five showing significant decreases in binge eating. We conclude that clinically supervised severe dietary energy restriction appears safe and beneficial for overweight or obese in iduals with pre-treatment binge eating disorder, and does not necessarily trigger binge eating in those without binge eating disorder.
Publisher: Wiley
Date: 28-05-2010
DOI: 10.1111/J.1463-1326.2009.01193.X
Abstract: Energy homeostasis is regulated by a complex interaction of molecules and pathways, and new antiobesity treatments are likely to require multiple pharmacological targeting of anorexigenic or orexigenic pathways to achieve effective loss of excess body weight and adiposity. Cannabinoids, acting via the cannabinoid-1 (CB1) receptor, and neuropeptide Y (NPY) are important modulators of feeding behaviour, energy metabolism and body composition. We investigated the interaction of CB1 and NPY in the regulation of energy homeostasis, hypothesizing that dual blockade of CB1 and NPY signalling will induce greater weight and/or fat loss than that induced by single blockade of either system alone. We studied the effects of the CB1 antagonist Rimonabant on food intake, body weight, body composition, energy metabolism and bone physiology in wild-type (WT) and NPY knockout (NPY(-/-)) mice. Rimonabant was administered orally at 10 mg/kg body weight twice per day for 3 weeks. Oral Rimonabant was delivered voluntarily to mice via a novel method enabling studies to be carried out in the absence of gavage-induced stress. Mice with dual blockade of CB1 and NPY signalling (Rimonabant-treated NPY(-/-) mice) exhibited greater reductions in body weight and adiposity than mice with single blockade of either system alone (Rimonabant-treated WT or vehicle-treated NPY(-/-) mice). These changes occurred without loss of lean tissue mass or bone mass. Furthermore, Rimonabant-treated NPY(-/-) mice showed a lower respiratory exchange ratio than that seen in Rimonabant-treated WT or vehicle-treated NPY(-/-) mice, suggesting that this additive effect of dual blockade of CB1 and NPY involves promotion of lipid oxidation. On the other hand, energy expenditure and physical activity were comparable amongst all treatment groups. Interestingly, Rimonabant similarly and transiently reduced spontaneous and fasting-induced food intake in WT and NPY(-/-) mice in the first hour after administration only, suggesting independent regulation of feeding by CB1 and NPY signalling. In contrast, Rimonabant increased serum corticosterone levels in WT mice, but this effect was not seen in NPY(-/-) mice, indicating that NPY signalling may be required for effects of CB1 on the hypothalamo-pituitary-adrenal axis. Dual blockade of CB1 and NPY signalling leads to additive reductions in body weight and adiposity without concomitant loss of lean body mass or bone mass. An additive increase in lipid oxidation in dual CB1 and NPY blockade may contribute to the effect on adiposity. These findings open new avenues for more effective treatment of obesity via dual pharmacological manipulations of the CB1 and NPY systems.
Publisher: Frontiers Media SA
Date: 22-03-2021
Abstract: Background: Previous research showed that weight-reducing diets increase appetite sensations and/or circulating ghrelin concentrations for up to 36 months, with transient or enduring perturbations in circulating concentrations of the satiety hormone peptide YY. Objective: This study assessed whether a diet that is higher in protein and low in glycemic index (GI) may attenuate these changes. Methods: 136 adults with pre-diabetes and a body mass index of ≥25 kg/m 2 underwent a 2-month weight-reducing total meal replacement diet. Participants who lost ≥8% body weight were randomized to one of two 34-month weight-maintenance diets: a higher-protein and moderate-carbohydrate (CHO) diet with low GI, or a moderate-protein and higher-CHO diet with moderate GI. Both arms involved recommendations to increase physical activity. Fasting plasma concentrations of total ghrelin and total peptide YY, and appetite sensations, were measured at 0 months (pre-weight loss), at 2 months (immediately post-weight loss), and at 6, 12, 24, and 36 months. Results: There was a decrease in plasma peptide YY concentrations and an increase in ghrelin after the 2-month weight-reducing diet, and these values approached pre-weight-loss values by 6 and 24 months, respectively ( P = 0.32 and P = 0.08, respectively, vs. 0 months). However, there were no differences between the two weight-maintenance diets. Subjective appetite sensations were not affected by the weight-reducing diet nor the weight-maintenance diets. While participants regained an average of ~50% of the weight they had lost by 36 months, the changes in ghrelin and peptide YY during the weight-reducing phase did not correlate with weight regain. Conclusion: A higher-protein, low-GI diet for weight maintenance does not attenuate changes in ghrelin or peptide YY compared with a moderate-protein, moderate-GI diet. Clinical Trial Registry: ClinicalTrials.gov registry ID NCT01777893 (PREVIEW) and ID NCT02030249 (Sub-study).
Publisher: Springer Science and Business Media LLC
Date: 05-12-2017
DOI: 10.1038/IJO.2017.258
Abstract: To test the potential efficacy of recombinant macrophage inhibitory cytokine-1 (MIC-1/GDF15) as an obesity therapeutic. Male C57BL/6 J mice, either fed on normal chow or high-fat diet for 16 weeks to induce diet-induced obesity, were infused with either recombinant MIC-1/GDF15 or vehicle for 34 days by osmotic minipump. During the experimental period metabolic parameters were measured. Blood and tissue were collected for analysis of inflammatory markers. MIC-1/GDF15 decreased food intake and body weight of high-fat-fed and chow-fed mice compared with their vehicle-treated control mice. MIC-1/GDF15 reduced body weight, accompanied by greater reduction in fat mass in high-fat-fed mice compared to its effect on chow-fed mice. Further, whilst MIC-1/GDF15-treated chow-fed mice lost lean as well as fat mass, MIC-1/GDF15-treated high-fat-fed mice lost fat mass alone. This reduction in body weight and adiposity was due largely to reduced food intake, but MIC-1/GDF15-treated high-fat-fed mice also displayed increased energy expenditure that may be due to increased thermogenesis. MIC-1/GDF15-treated high-fat-fed mice also had higher circulating level of adiponectin and lower tissue expression, and circulating levels of leptin and inflammatory mediators associated with insulin resistance. Peripheral insulin and glucose intolerance were improved in both MIC-1/GDF15-treated high-fat-fed and chow-fed mice compared to that of their vehicle-treated control mice. MIC-1/GDF15 is highly effective in reducing adiposity and correcting the metabolic dysfunction of mice with high-fat fed. These studies suggest that MIC-1/GDF15 may be a candidate anti-obesity therapeutic.
Publisher: Elsevier BV
Date: 03-2006
Publisher: Informa UK Limited
Date: 1993
DOI: 10.3109/08977199308991591
Abstract: J2E erythroid cells proliferate and differentiate in response to erythropoietin (epo), the red blood cell specific hormone. Using methylcellulose colony assays and suspension cultures we have demonstrated that nearly all the cells stimulated by epo synthesized haemoglobin. To achieve maximum production of haemoglobin J2E cells had to be treated with epo for only 6 h hormone added subsequently did not enhance haemoglobin synthesis. Although virtually all viable J2E cells produced haemoglobin, the cells matured morphologically at different rates. Thus, upon exposure to epo J2E cells become committed to erythroid terminal differentiation but proceed in an asynchronous manner.
Publisher: Informa UK Limited
Date: 03-2007
Abstract: The neuropeptide Y system - comprising neuropeptide Y, peptide YY, pancreatic polypeptide and the Y receptors through which they act (Y1, Y2, Y4, Y5 and y6) - has been at the center of attention with regards to regulation of feeding behavior and its possible involvement in obesity. In the past, research has focused mainly on the orexigenic and obesogenic action of this system, with Y1 and Y5 receptors being prime candidates as mediators of neuropeptide Y-induced hyperphagia and obesity. However, in recent years, the role of other members of the neuropeptide Y family, peptide YY, pancreatic polypeptide and the Y2 and Y4 receptors through which they predominantly act, have commanded increasing attention on account of their effects to mediate satiety and promote weight loss via actions in key brain structures, such as the arcuate nucleus of the hypothalamus and the brain stem. This review focuses on the role of peptide YY- and pancreatic polypeptide-like compounds as possible antiobesity drugs, taking into account their effects, not only on energy balance, but also in the regulation of bone formation, and highlights potential benefits of using Y2 and/or Y4 antagonists (as opposed to agonists such as peptide YY or pancreatic polypeptide) in the treatment of obesity.
Publisher: Walter de Gruyter GmbH
Date: 21-08-2013
Abstract: Obesity treatments aim to maximize fat loss, particularly abdominal or visceral fat, without compromising lean or bone mass. However, the literature contains numerous ex les of obesity treatments that – in addition to fat loss – result in loss of lean mass and/or bone mass. Because of the known effects of energy restriction to increase activity of the hypothalamo-pitutiary adrenal (HPA) axis in lean humans and animals, and because increases in circulating glucocorticoid levels could potentially contribute to adverse body compositional changes with obesity treatments, we conducted a systematic PubMed search to determine whether HPA axis activation also occurs in response to energy restriction in obese humans and animals. In most studies in obese humans, short-term severe energy restriction increased circulating cortisol levels, and this response was also seen in two longer-term human studies involving severe or moderate energy restriction. These findings parallel studies on short- or long-term energy restriction in obese rodents, with most studies showing increases in circulating corticosterone concentrations, and no change or actual increases in hypothalamic expression of corticotropin-releasing hormone, urocortin 3 or their receptors. However, a significant proportion of studies involving longer-term severe or moderate energy restriction in obese humans showed no change or decreases in HPA axis function. There was variability among human studies in the duration of energy restriction and timing of the HPA axis investigations (i.e., during energy restriction, or after a period of post-restriction weight maintenance). In order to unambiguously determine changes in HPA axis function with energy restriction in obese humans, it will be important to assess HPA axis function at multiple time points
Publisher: Elsevier BV
Date: 12-2002
Abstract: The co-ordinated regulation of food intake and energy expenditure takes place in the hypothalamic regions of the brain. Current understanding of the systems involved in this regulation suggests that, in the hypothalamus, there are two major groups of neuropeptides involved in orexigenic and anorexic processes. The orexigenic neuropeptides are neuropeptide Y (NPY) and agouti-related peptide (AgRP) and the anorexic neuropeptides are alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine and hetamine-related transcript (CART). Theneurons expressing these neuropeptides interact with each other and with signals from the periphery (such as leptin, insulin, ghrelin and glucocorticoids) to regulate feeding behaviour, energy expenditure and various endocrine axes. Although direct evidence is limited, there are ex les of genetic obesity in humans which suggest that the balance between orexigenic and anorexic pathways in the hypothalamus is also pivotally important in the maintenance of energy homeostasis in humans.
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.NPEP.2011.07.009
Abstract: Weight loss inhibits thyrotropic function and reduces metabolic rate, thereby contributing to weight regain. Under negative energy balance there is an increase in the hypothalamic expression of both neuropeptide Y (NPY) and agouti related peptide (AgRP), the endogenous antagonist of melanocortin 4 (MC4) receptors. Both NPY and MC4 receptor antagonism reduce thyrotropic function centrally, but it is not known whether these pathways operate by similar or distinct mechanisms. We compared the time-course of effects of acute or chronic intracerebroventricular (ICV) administration of NPY (1.2 nmol acute bolus, or 3.5 nmol/day for 6 days) or the MC4 receptor antagonist HS014 (1.5 nmol bolus, or 4.8 nmol/day) on plasma concentrations of thyroid stimulating hormone (TSH) or free thyroxine (T4) in male rats pair-fed with vehicle-infused controls. These doses equipotently induced hyperphagia in acute studies, reduced latency to feed, and increased white adipose tissue mass after 6 days of infusion. Acute central NPY but not HS014 administration significantly reduced plasma TSH concentrations within 30-60 min and plasma free T4 levels within 90-120 min. These inhibitory effects were sustained for up to 5-6 days of continuous NPY infusion. HS014 induced a transient decrease in plasma free T4 levels that was observed only after 1-2 days of continuous ICV infusion. While both NPY and HS014 significantly increased corticosteronemia within an hour after ICV injection, the effect of NPY was significantly more pronounced and was sustained for up to 4 days of administration. Both NPY and HS014 significantly decreased the brown adipose tissue protein levels of uncoupling protein-3. We conclude that central NPY and MC4 antagonism decrease thyrotropic function via partially distinct mechanisms with different time courses, possibly involving glucocorticoid effects of NPY. MC4 receptor antagonism increases adiposity via pathways independent of increased food intake or changes in circulating concentrations of TSH, free T4 or corticosterone.
Publisher: Public Library of Science (PLoS)
Date: 10-07-2023
DOI: 10.1371/JOURNAL.PONE.0282401
Abstract: The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify in idual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and in idual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.CMET.2013.01.006
Abstract: Neuropepetide Y (NPY) is best known for its powerful stimulation of food intake and its effects on reducing energy expenditure. However, the pathways involved and the regulatory mechanisms behind this are not well understood. Here we demonstrate that NPY derived from the arcuate nucleus (Arc) is critical for the control of sympathetic outflow and brown adipose tissue (BAT) function. Mechanistically, a key change induced by Arc NPY signaling is a marked Y1 receptor-mediated reduction in tyrosine hydroxylase (TH) expression in the hypothalamic paraventricular nucleus (PVN), which is also associated with a reduction in TH expression in the locus coeruleus (LC) and other regions in the brainstem. Consistent with this, Arc NPY signaling decreased sympathetically innervated BAT thermogenesis, involving the downregulation of uncoupling protein 1 (UCP1) expression in BAT. Taken together, these data reveal a powerful Arc-NPY-regulated neuronal circuit that controls BAT thermogenesis and sympathetic output via TH neurons.
Publisher: AIP Publishing
Date: 26-09-2016
DOI: 10.1063/1.4963649
Abstract: Attenuation based X-ray micro computed tomography (XCT) provides three-dimensional images with micrometer resolution. However, there is a trade-off between the smallest size of the structures that can be resolved and the measurable s le size. In this letter, we present an imaging method using a compact laboratory setup that reveals information about micrometer-sized structures within s les that are several orders of magnitudes larger. We combine the anisotropic dark-field signal obtained in a grating interferometer and advanced tomographic reconstruction methods to reconstruct a six dimensional scattering tensor at every spatial location in three dimensions. The scattering tensor, thus obtained, encodes information about the orientation of micron-sized structures such as fibres in composite materials or dentinal tubules in human teeth. The sparse acquisition schemes presented in this letter enable the measurement of the full scattering tensor at every spatial location and can be easily incorporated in a practical, commercially feasible laboratory setup using conventional X-ray tubes, thus allowing for widespread industrial applications.
Publisher: Wiley
Date: 10-2006
DOI: 10.1359/JBMR.060705
Abstract: NeuropeptideY-, Y2 receptor (Y2)-, and leptin-deficient mice show similar anabolic action in cancellous bone but have not been assessed in cortical bone. Cortical bone mass is elevated in Y2(-/-) mice through greater osteoblast activity. In contrast, leptin deficiency results in reduced bone mass. We show opposing central regulation of cortical bone. Treatment of osteoporosis is confounded by a lack of agents capable of stimulating the formation of bone by osteoblasts. Recently, the brain has been identified as a potent anabolic regulator of bone formation. Hypothalamic leptin or Y2 receptor signaling are known to regulate osteoblast activity in cancellous bone. However, assessment of these pathways in the structural cortical bone is critical to understanding their role in skeletal health and their potential clinical relevance to osteoporosis and its treatment. Long bones of 16-week male ob/ob and germline and hypothalamic Y2(-/-) mice were assessed by QCT. Cortical osteoblast activity was assessed histologically. The femora of skeletally mature Y2(-/-) mice and of leptin-deficient ob/ob and Y2(-/-)ob/ob mice were assessed for changes in cortical osteoblast activity and bone mass. Ablation of Y2 receptors increased osteoblast activity on both endosteal and periosteal surfaces, independent of leptin, resulting in increased cortical bone mass and density in Y2(-/-) mice along the entire femur. Importantly, these changes were evident after deletion of hypothalamic Y2 receptors in adult mice, with a 5-fold elevation in periosteal bone formation. This is in marked contrast to leptin-deficient models that displayed reduced cortical mass and density. These changes were associated with substantial differences in calculated strength between the Y2(-/-) and leptin-deficient mice. These results indicate that the Y2-mediated anabolic pathway stimulates cortical and cancellous bone formation, whereas the leptin-mediated pathway has opposing effects in cortical and cancellous bone, diminishing the production of cortical bone. The findings from conditional hypothalamic Y2 knockout show a novel, inducible control mechanism for cortical bone formation and a potential new pathway for anabolic treatment of osteoporosis.
Publisher: Cambridge University Press (CUP)
Date: 15-02-2023
DOI: 10.1017/S0954422423000045
Abstract: The cornerstone of obesity treatment is behavioural weight management, resulting in significant improvements in cardio-metabolic and psychosocial health. However, there is ongoing concern that dietary interventions used for weight management may precipitate the development of eating disorders. Systematic reviews demonstrate that, while for most participants medically supervised obesity treatment improves risk scores related to eating disorders, a subset of people who undergo obesity treatment may have poor outcomes for eating disorders. This review summarises the background and rationale for the formation of the Eating Disorders In weight-related Therapy (EDIT) Collaboration. The EDIT Collaboration will explore the complex risk factor interactions that precede changes to eating disorder risk following weight management. In this review, we also outline the programme of work and design of studies for the EDIT Collaboration, including expected knowledge gains. The EDIT studies explore risk factors and the interactions between them using in idual-level data from international weight management trials. Combining all available data on eating disorder risk from weight management trials will allow sufficient s le size to interrogate our hypothesis: that in iduals undertaking weight management interventions will vary in their eating disorder risk profile, on the basis of personal characteristics and intervention strategies available to them. The collaboration includes the integration of health consumers in project development and translation. An important knowledge gain from this project is a comprehensive understanding of the impact of weight management interventions on eating disorder risk.
Publisher: Public Library of Science (PLoS)
Date: 27-06-2014
Publisher: MDPI AG
Date: 24-02-2019
DOI: 10.3390/NU11020478
Abstract: Background: Ramadan involves one month of fasting from sunrise to sunset. In this meta-analysis, we aimed to determine the effect of Ramadan fasting on weight and body composition. Methods: In May 2018, we searched six databases for publications that measured weight and body composition before and after Ramadan, and that did not attempt to influence physical activity or diet. Results: Data were collected from 70 publications (90 comparison groups, 2947 participants). There was a significant positive correlation between starting body mass index and weight lost during the fasting period. Consistently, there was a significant reduction in fat percentage between pre-Ramadan and post-Ramadan in people with overweight or obesity (−1.46 (95% confidence interval: −2.57 to −0.35) %, p = 0.010), but not in those of normal weight (−0.41 (−1.45 to 0.63) %, p = 0.436). Loss of fat-free mass was also significant between pre-Ramadan and post-Ramadan, but was about 30% less than loss of absolute fat mass. At 2–5 weeks after the end of Ramadan, there was a return towards, or to, pre-Ramadan measurements in weight and body composition. Conclusions: Even with no advice on lifestyle changes, there are consistent—albeit transient—reductions in weight and fat mass with the Ramadan fast, especially in people with overweight or obesity.
Publisher: Wiley
Date: 09-05-2015
DOI: 10.1002/OBY.21041
Abstract: In iduals with Prader-Willi syndrome (PWS) are commonly restricted to 60-75% of height-appropriate calorie intake because they rapidly become obese on a normal diet. This study measured changes in energy expenditure, glucose and lipid homeostasis, and metabolic flexibility in response to a meal in PWS adults. 11 adults with PWS were compared with 12 adiposity-matched and 10 lean subjects. Indirect calorimetry was conducted at baseline and 210 min after a standardized 600 kCal breakfast to assess energy expenditure and substrate utilization. Circulating glucose, insulin, C-peptide, glucagon, nonesterified fatty acids, and triglycerides were measured up to 240 min. Insulin sensitivity and insulin secretion rate were assessed by HOMA-IR and C-peptide deconvolution, respectively. Body composition was determined by dual-energy X-ray absorptiometry. The PWS group had lower lean mass than the obesity control group. Corrected for lean mass, there were no differences between the PWS and obesity groups in resting metabolic rate or metabolic flexibility. Total and abdominal fat mass, insulin sensitivity, and insulin secretion rate were also similar between these groups. This study did not detect an intrinsic metabolic defect in in iduals with PWS. Rather, lower lean mass, combined with lower physical activity, may contribute to weight gain on an apparent weight-maintenance diet.
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.NUT.2008.06.019
Abstract: Neuropeptide Y regulates numerous processes including food intake, body composition, and reproduction by at least five different Y receptors. We previously demonstrated a synergistic interaction between Y2 and Y4 receptors in reducing adiposity in chow- or fat-fed Y2Y4-receptor double-knockout mice. In the present study, we investigated whether this synergy could reduce the massive obesity of leptin-deficient ob/ob mice. Mice with germline deletions of Y2 and Y4 receptors were crossed onto the ob/ob strain. Body weight was measured weekly until 15-18 wk of age before decapitation for collection of trunk blood and tissues. Male and female Y24ob triple mutants showed highly significant reductions in body weight and white adipose tissue mass compared with ob/ob mice. This reduction in body weight was not evident in Y2ob or Y4ob double mutants, and the effect on adiposity was significantly greater than that seen in Y2ob or Y4ob mice. These changes were associated with significant attenuation of the increased brown adipose tissue mass and small intestinal hypertrophy seen in ob/ob mice and with normalization of the low circulating free thyroxine concentrations seen in female ob/ob mice and the high circulating corticosterone concentrations seen in male ob/ob mice. These data reveal a synergistic interaction between Y2 and Y4 receptors in attenuating the massive obesity of ob/ob mice, possibly mediated by stimulation of thyroid function and inhibition of intestinal nutrient absorption. Dual pharmacologic antagonism of Y2 and Y4 receptors could help people to attain and maintain a healthy weight.
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1016/J.NEUROPHARM.2006.07.006
Abstract: Antipsychotic drugs have been used effectively for the treatment of schizophrenia symptoms, but they are often associated with metabolic side effects such as weight gain and endocrine disruptions. To investigate the possible mechanisms of antipsychotic-induced metabolic effects, we studied the impact of chronic administration of a typical antipsychotic drug (haloperidol) and an atypical antipsychotic (risperidone) to male rats on food intake, body weight, adiposity, and the circulating concentrations of hormones and metabolites that can influence energy homeostasis. Chronic (28days) haloperidol administration had no effect on food intake, weight gain or adiposity in male rats, whereas risperidone treatment resulted in a transient reduction in food intake and significantly reduced body weight gain compared to vehicle-treated control rats. Whereas neither antipsychotic had any effect on serum lipid profiles, glucose tolerance or the circulating concentrations of hormones controlled by the hypothalamo-pituitary-thyroid (free T4), -adrenal (corticosterone), -somatotropic (IGF-1), or -gonadotropic axes (testosterone), haloperidol increased circulating insulin levels and risperidone increased serum glucagon levels. This finding suggests that haloperidol or risperidone induce distinct metabolic effects. Since metabolic disorders such as obesity and type 2 diabetes mellitus represent serious health issues, understanding antipsychotic-induced endocrine and metabolic effects may ultimately allow better control of these side effects.
Publisher: MDPI AG
Date: 15-09-2021
DOI: 10.3390/NU13093200
Abstract: About half of Australian women have a body mass index in the overweight or obese range at the start of pregnancy, with serious consequences including preterm birth, gestational hypertension and diabetes, caesarean section, stillbirth, and childhood obesity. Trials to limit weight gain during pregnancy have had limited success and reducing weight before pregnancy has greater potential to improve outcomes. The PreBabe Pilot study was a randomised controlled pilot trial to assess the feasibility, acceptability and potential weight loss achieved using a commercial online partial meal replacement program, (MR) vs. telephone-based conventional dietary advice, (DA) for pre-conception weight-loss over a 10-week period. Women 18–40 years of age with a BMI ≥ 25 kg/m2 planning pregnancy within the next 6 to 12 months were included in the study. All participants had three clinic visits with a dietitian and one obstetric consultation. In total, 50 women were enrolled in the study between June 2018 and October 2019–26 in MR and 24 in DA. Study retention at the end of 10 week intervention 81% in the MR arm and 75% in the DA arm. In the-intention-to-treat analysis, women using meal replacements lost on average 5.4 ± 3.1% body weight compared to 2.3 ± 4.2% for women receiving conventional advice (p = 0.029). Over 80% of women in the MR arm rated the support received as excellent, compared to 39% in the DA arm (p 0.001). Women assigned to the MR intervention were more likely to achieve pregnancy within 12 months of the 10 week intervention (57% (12 of 21) women assigned to MR intervention vs. 22% (4 of 18) assigned to the DA group (p = 0.049) became pregnant). The findings suggest that a weight loss intervention using meal replacements in the preconception period was acceptable and may result in greater weight loss than conventional dietary advice alone.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.ORCP.2016.03.004
Abstract: Identifying in iduals who are less likely to respond to a weight loss intervention allows better allocation or focus of resources to achieve better weight loss results. The current study investigated whether baseline levels of mindfulness would predict weight loss during a 12-month diet and exercise intervention. The Five Facet Mindfulness Questionnaire (FFMQ) was administered and body weight measured, at baseline, three, six and 12 months in 140 participants with pre-diabetes or type 2 diabetes mellitus and a body mass index of ≥25kg/m There was no correlation between baseline mindfulness scores and weight loss. Mean baseline total FFMQ score was 112.2 [95% confidence interval: 109.4, 115.1] which did not change over the course of the study. Mean baseline body weight was 95.1kg (standard deviation (19.1kg)). There was a significant decrease in weight at month 12 (-3.8kg (±standard deviation 5.8kg)). This is comparable to the weight loss achieved by participants in other interventions of the same duration. The findings suggest that baseline dispositional mindfulness does not predict the amount of weight loss in a lifestyle (diet and exercise) intervention.
Publisher: MDPI AG
Date: 07-12-2019
DOI: 10.3390/BS9120144
Abstract: Severely energy-restricted diets are used in obesity management, but their efficacy in people with class III obesity (body mass index ≥40 kg/m2) is uncertain. The aims of this systematic review and meta-analysis were to determine the effectiveness and characteristics of severely energy-restricted diets in people with class III obesity. As there was a lack of publications reporting long-term dietary interventions and randomised controlled trial designs, our original publication inclusion criteria were broadened to include uncontrolled study designs and a higher upper limit of energy intake. Eligible publications reported studies including adults with class III obesity and that assessed a diet with daily energy intake ≤5000 kJ for ≥4 weeks. Among 572 unique publications from 4 databases, 11 were eligible and 10 were suitable for meta-analysis. Our original intention was to classify comparison arms into short-term ( months) and long-term ( year) interventions. Due to the lack of long-term data found, comparison arms were classified according to the commonalities in dietary intervention length among the included publications, namely dietary interventions of 4 weeks’ duration and those of ≥6 weeks’ duration. After a 4-week severely energy-restricted diet intervention, the pooled average weight loss was 9.81 (95% confidence interval 10.80, 8.83) kg, with a 95% prediction interval of 6.38 to 13.25 kg, representing a loss of approximately 4.1 to 8.6% of initial body weight. Diets ≥6 weeks’ duration produced 25.78 (29.42, 22.15) kg pooled average weight loss, with a 95% prediction interval of 13.77 to 37.80 kg, representing approximately 10.2 to 28.0% weight loss. Daily dietary prescriptions ranged from 330 to 5000 kJ (mean ± standard deviation 2260 ± 1400 kJ), and had wide variations in macronutrient composition. The diets were administered mostly via liquid meal replacement products. While the included publications had a moderate risk of bias score, which may inflate reported weight loss outcomes, the published data to date suggest that severely energy-restricted diets, delivered via diets of varying composition, effectively produce clinically relevant weight loss (≥10% of initial body weight) when used for 6 weeks or more in people with class III obesity.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2022
DOI: 10.1038/S41366-021-01046-3
Abstract: To describe the association between body weight change and the risk of knee replacement and hip replacement. Time-to-event survival analysis from a population-based cohort of participants who had or were at risk of clinically significant knee osteoarthritis at baseline. Data from the Osteoarthritis Initiative (OAI), which collected data from four clinical centres in the United States. A total of 8069 knees from 4081 participants, and 8076 hips from 4064 participants (59.3% female) aged 45-79 years, with mean ± SD body mass index (BMI) of 28.7 ± 4.8 kg/m Body weight change from baseline as a percentage of baseline at repeated follow-up visits over 8 years. Incidence of primary knee or hip replacement during 8-year follow-up. Body weight change had a small, positive, linear association with the risk of knee replacement (adjusted hazard ratio [HR] 1.02 95% confidence interval [CI] 1.00-1.04). Body weight change was also positively and linearly associated with the risk of hip replacement in hips that were persistently painful at baseline (adjusted HR 1.03 95% CI 1.01-1.05), but not in hips that were not persistently painful at baseline. There were no significant interactions between body weight change and baseline BMI in the association with knee or hip replacement. In people with or at risk of clinically significant knee osteoarthritis, every 1% weight loss was associated with a 2% reduced risk of knee replacement and - in those people who also had one or more persistently painful hips - a 3% reduced risk of hip replacement, regardless of baseline BMI. Public health strategies that incorporate weight loss interventions have the potential to reduce the burden of knee and hip replacement surgery.
Publisher: Wiley
Date: 24-08-2018
DOI: 10.1111/OBR.12715
Abstract: Although very low energy diets (VLEDs) are the most successful non-surgical, non-pharmacological treatment for obesity, they are underutilized, and little is known about experiences of people using VLEDs for weight loss. This systematic review synthesizes qualitative studies investigating participants' experiences of undertaking a VLED composed of total meal replacement products to lose weight. Of the 4,911 articles screened, three studies met criteria for inclusion. Thematic synthesis was used to analyse the study findings. Health and appearance were the main motivators to use a VLED for weight loss. Adherence was facilitated by group support meetings, rapid weight loss and ease of use of the diet. Being part of a clinical trial gave a sense of accountability and further reason to adhere to a VLED, and the VLED itself was well accepted by users. Barriers to adherence, such as temptations and social occasions, were overcome by avoidance and distraction strategies. In conclusion, this qualitative synthesis of users' experiences of VLEDs shows that VLEDs are well accepted and positively viewed by users. More in-depth research could facilitate understanding of how this weight loss strategy influences the weight maintenance period, in order to facilitate better long-term results.
Publisher: American Diabetes Association
Date: 02-1997
Publisher: American Diabetes Association
Date: 04-1997
Publisher: Springer Science and Business Media LLC
Date: 16-07-2011
DOI: 10.1007/S12031-010-9423-0
Abstract: Both the neuropeptide Y (NPY) and the leptin systems have been shown to be important central mediators of bone metabolism. However, the interaction between these two systems is complex and not fully understood. Here, we show that a unique interaction exists between Y2 and Y4 receptors in the regulation of bone homeostasis that is not evident when combined with lack of Y1 signalling. Despite the hypoleptinaemia shown in male Y2/Y4 double knockout (Y2⁻/⁻ Y4⁻/⁻) mice, when on the leptin-deficient ob/ob background, these mice display reduced cancellous bone mass. However, combined Y2/Y4 deletion enhances the effect of leptin deficiency on the cortical bone compartment. By replicating the enhanced central NPY expression evident in ob/ob mice using virally mediated overexpression of NPY in the hypothalamus of Y receptor knockout mice, we demonstrate that Y2⁻/⁻ Y4⁻/⁻ mice have an exaggerated response to the anti-osteogenic effects of elevated hypothalamic NPY in both cancellous and cortical bone and that this effect appears to be dependent on Y1 receptor signalling. This study highlights the complex interaction between Y receptors in the control of bone mass. Moreover, it suggests that the reduction in cortical bone observed in the absence of leptin is due to the anti-osteogenic effect of elevated hypothalamic NPY levels.
Publisher: Elsevier BV
Date: 06-2017
Publisher: MDPI AG
Date: 07-2019
DOI: 10.3390/BS9070072
Abstract: The prevalence of obesity with comorbid binge eating behaviour is growing at a faster rate than that seen for either obesity or eating disorders as separate conditions. Approximately 6% of the population are affected and they potentially face a lifetime of poor physical and mental health outcomes and an inability to sustain long-term weight loss. Current treatment options are inadequate in that they typically address either obesity or eating disorders exclusively, not the combination of both conditions. By treating one condition without treating the other, relapse is common, and patients are often left disappointed with their lack of weight loss. An integrated approach to treating these in iduals is needed to prevent a worsening of the comorbidities associated with excess body weight and eating disorders. A new therapy has recently been developed, named HAPIFED, which addresses both overweight/obesity and comorbid binge eating behaviour with the combination of behavioural weight loss therapy and cognitive behaviour therapy-enhanced (CBT-E). The aim of this paper is to document the protocol for the Real Happy Study, which will evaluate the effectiveness of the HAPIFED program in treating overweight or obesity with comorbid binge-eating behaviour in a real-world setting.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-02-2021
DOI: 10.1249/MSS.0000000000002636
Abstract: Can intermittent energy restriction (IER) improve fat loss and fat-free mass retention compared with continuous energy restriction (CER) in resistance-trained adults? Sixty-one adults (32 women) with a mean (SD) age of 28.7 (6.5) yr, body weight of 77.2 (16.1) kg, and body fat of 25.5% (6.1%) were randomized to 12 wk of 1) 4 × 3 wk of moderate (m) energy restriction interspersed with 3 × 1 wk of energy balance (mIER n = 30 15 wk total) or 2) 12 wk of continuous moderate energy restriction (mCER n = 31). Analyses of all outcome measures were by intention-to-treat. After accounting for baseline differences, mIER did not result in lower fat mass or body weight, or greater fat-free mass, compared with mCER after energy restriction. Mean (and 97.5% confidence interval for fat mass at the end of mIER versus mCER was 15.3 (12.5–18.0) kg versus 18.0 (14.3–21.7) kg ( P = 0.321), that for fat-free mass was 56.7 (51.5–61.9) kg versus 56.7 (51.4–62.0) kg ( P = 0.309), and that for body weight (with 95% confidence interval) was 72.1 (66.4–77.9) versus 74.6 (69.3–80.0) ( P = 0.283). There were no differences between interventions in muscle strength or endurance or in resting energy expenditure, leptin, testosterone, insulin-like growth factor-1, free 3,3′,5-triiodothyronine or active ghrelin, or in sleep, muscle dysmorphia, or eating disorder behaviors. However, participants in mIER exhibited lower hunger ( P = 0.002) and desire to eat ( P = 0.014) compared with those in mCER, and greater satisfaction ( P = 0.016) and peptide YY ( P = 0.034). Similar fat loss and fat-free mass retention are achieved with mIER and mCER during 12 wk of energy restriction however, mIER is associated with reduced appetite.
Publisher: Public Library of Science (PLoS)
Date: 06-07-2012
Publisher: Wiley
Date: 18-03-2013
DOI: 10.1002/JBMR.1786
Abstract: Leptin signaling is required for normal bone homeostasis however, loss of leptin results in differing effects on cortical and cancellous bone, as well as altered responses between the axial and appendicular regions. Local β-adrenergic actions are responsible for the greater cancellous bone volume in leptin-deficient (ob/ob) mice however, the mechanism responsible for the opposing reduction in cortical bone in ob/ob mice is not known. Here we show that blocking the leptin-deficient increase in neuropeptide Y (NPY) expression reverses the cortical bone loss in ob/ob mice. Mice null for both NPY and leptin (NPY(-/-) ob/ob), display greater cortical bone mass in both long-bones and vertebra, with NPY(-/-) ob/ob mice exhibiting thicker and denser cortical bone, associated with greater endocortical and periosteal mineral apposition rate (MAR), compared to ob/ob animals. Importantly, these cortical changes occurred without significant increases in body weight, with NPY(-/-) ob/ob mice showing significantly reduced adiposity compared to ob/ob controls, most likely due to the reduced respiratory exchange ratio seen in these animals. Interestingly, cancellous bone volume was not different between NPY(-/-) ob/ob and ob/ob, suggesting that NPY is not influencing the adrenergic axis. Taken together, this work demonstrates the critical role of NPY signaling in the regulation of bone and energy homeostasis, and more importantly, suggests that reduced leptin levels or leptin resistance, which occurs in obesity, could potentially inhibit cortical bone formation via increased central NPY signaling.
Publisher: AME Publishing Company
Date: 04-0044
Publisher: MDPI AG
Date: 27-06-2018
DOI: 10.3390/NU10070829
Publisher: Elsevier BV
Date: 12-2018
Publisher: Elsevier BV
Date: 05-2009
Start Date: 1989
End Date: 1994
Funder: Swiss National Science Foundation
View Funded ActivityStart Date: 1994
End Date: 1997
Funder: Swiss National Science Foundation
View Funded ActivityStart Date: 2018
End Date: 2022
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2020
End Date: 2025
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2017
End Date: 2021
Funder: National Health and Medical Research Council
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