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Find video protocols related to scientific articles indexed in Pubmed.
Meal frequency and timing in health and disease.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-19-2014
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Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population.
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Effects of exercise training in women with polycystic ovary syndrome on adipose expression of perilipin 3.
Eur. J. Endocrinol.
PUBLISHED: 10-25-2014
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Objective: Polycystic Ovary Syndrome (PCOS) is associated with reduced adipose tissue lipolysis that can be rescued by aerobic exercise. We aimed to identify differences in gene expression of perilipins and associated targets in adipose tissue in women with PCOS before and after exercise. Design and Methods: We conducted a cross-sectional study in 8 women with PCOS and 8 women matched for BMI and age with normal cycles. Women with PCOS also completed a 16-week prospective aerobic exercise-training study. Abdominal subcutaneous adipose tissue biopsies were collected, and primary adipose-derived stromal/stem cell cultures were established from women with PCOS before 16 weeks of aerobic exercise training (n=5) and controls (n=5). Gene expression was measured using real time PCR, in vitro lipolysis was measured using radiolabeled oleate, and PLIN3 protein content was measured by western blotting. Results: The expression of PLIN1, PLIN3, and PLIN5, along with coatomers ARF1, ARFRP1, and ?COP were ~80% lower in women with PCOS (all p<0.05). Following exercise training, PLIN3 was the only perilipin to increase significantly (p<0.05), along with coatomers ARF1, ARFRP1, ?COP, and Sec23a (all p<0.05). Furthermore, PLIN3 protein expression was undetectable in the cell cultures from women with PCOS vs. controls. Following exercise training, in vitro adipose oleate oxidation, glycerol secretion, and PLIN3 protein expression were increased, along with reductions in triglyceride content and absence of large lipid droplet morphology. Conclusions: These findings suggest that PLIN3 and coatomer GTPases are important regulators of lipolysis and triglyceride storage in the adipose tissue of women with PCOS.
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Relationship between whole-body macronutrient oxidative partitioning and pancreatic insulin secretion/?-cell function in non-diabetic humans.
Metab. Clin. Exp.
PUBLISHED: 08-07-2014
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Glucose-stimulated insulin secretion correlates inversely with the degree of whole-body insulin sensitivity suggesting a crosstalk between peripheral organs and pancreas. Such sensing mechanism could be mediated by changes in glucose flux (uptake, oxidation or storage) in peripheral tissues that may drive insulin secretion.
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An objective estimate of energy intake during weight gain using the intake-balance method.
Am. J. Clin. Nutr.
PUBLISHED: 07-23-2014
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Estimates of energy intake (EI) in humans have limited validity.
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Effect of 8 weeks of overfeeding on ectopic fat deposition and insulin sensitivity: testing the "adipose tissue expandability" hypothesis.
Diabetes Care
PUBLISHED: 07-10-2014
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The presence of large subcutaneous adipocytes in obesity has been proposed to be linked with insulin resistance and type 2 diabetes through the "adipose tissue expandability" hypothesis, which holds that large adipocytes have a limited capacity for expansion, forcing lipids to be stored in nonadipose ectopic depots (skeletal muscle, liver), where they interfere with insulin signaling. This hypothesis has, however, been largely formulated by cross-sectional findings and to date has not been prospectively demonstrated in the development of insulin resistance in humans.
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Caveolin-1 expression and cavin stability regulate caveolae dynamics in adipocyte lipid store fluctuation.
Diabetes
PUBLISHED: 06-26-2014
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Adipocytes specialized in the storage of energy as fat are among the most caveolae-enriched cell types. Loss of caveolae produces lipodystrophic diabetes in humans, which cannot be reversed by endothelial rescue of caveolin expression in mice, indicating major importance of adipocyte caveolae. However, how caveolae participate in fat cell functions is poorly understood. We investigated dynamic conditions of lipid store fluctuations and demonstrate reciprocal regulation of caveolae density and fat cell lipid droplet storage. We identified caveolin-1 expression as a crucial step in adipose cell lines and in mice to raise the density of caveolae, to increase adipocyte ability to accommodate larger lipid droplets, and to promote cell expansion by increased glucose utilization. In human subjects enrolled in a trial of 8 weeks of overfeeding to promote fattening, adipocyte expansion response correlated with initial caveolin-1 expression. Conversely, lipid mobilization in cultured adipocytes to induce lipid droplet shrinkage led to biphasic response of cavin-1 with ultimate loss of expression of cavin-1 and -3 and EHD2 by protein degradation, coincident with caveolae disassembly. We have identified the key steps in cavin/caveolin interplay regulating adipocyte caveolae dynamics. Our data establish that caveolae participate in a unique cell response connected to lipid store fluctuation, suggesting lipid-induced mechanotension in adipocytes.
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Total body skeletal muscle mass: estimation by creatine (methyl-d3) dilution in humans.
J. Appl. Physiol.
PUBLISHED: 04-24-2014
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Current methods for clinical estimation of total body skeletal muscle mass have significant limitations. We tested the hypothesis that creatine (methyl-d3) dilution (D3-creatine) measured by enrichment of urine D3-creatinine reveals total body creatine pool size, providing an accurate estimate of total body skeletal muscle mass. Healthy subjects with different muscle masses [n = 35: 20 men (19-30 yr, 70-84 yr), 15 postmenopausal women (51-62 yr, 70-84 yr)] were housed for 5 days. Optimal tracer dose was explored with single oral doses of 30, 60, or 100 mg D3-creatine given on day 1. Serial plasma samples were collected for D3-creatine pharmacokinetics. All urine was collected through day 5. Creatine and creatinine (deuterated and unlabeled) were measured by liquid chromatography mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DXA), and traditional 24-h urine creatinine. D3-creatine was rapidly absorbed and cleared with variable urinary excretion. Isotopic steady-state of D3-creatinine enrichment in the urine was achieved by 30.7 ± 11.2 h. Mean steady-state enrichment in urine provided muscle mass estimates that correlated well with MRI estimates for all subjects (r = 0.868, P < 0.0001), with less bias compared with lean body mass assessment by DXA, which overestimated muscle mass compared with MRI. The dilution of an oral D3-creatine dose determined by urine D3-creatinine enrichment provides an estimate of total body muscle mass strongly correlated with estimates from serial MRI with less bias than total lean body mass assessment by DXA.
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Weight gain reveals dramatic increases in skeletal muscle extracellular matrix remodeling.
J. Clin. Endocrinol. Metab.
PUBLISHED: 03-06-2014
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In animal models of obesity, chronic inflammation and dysregulated extracellular matrix remodeling in adipose tissue leads to insulin resistance. Whether similar pathophysiology occurs in humans is not clear.
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Determinants of sedentary 24-h energy expenditure: equations for energy prescription and adjustment in a respiratory chamber.
Am. J. Clin. Nutr.
PUBLISHED: 02-05-2014
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Achieving energy balance is critical for the interpretation of results obtained in respiratory chambers. However, 24-h energy expenditure (24EE) predictions based on estimated resting metabolic rate and physical activity level are often inaccurate and imprecise.
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Metabolic adaptation following massive weight loss is related to the degree of energy imbalance and changes in circulating leptin.
Obesity (Silver Spring)
PUBLISHED: 01-30-2014
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To measure changes in resting metabolic rate (RMR) and body composition in obese subjects following massive weight loss achieved via bariatric surgery or calorie restriction plus vigorous exercise.
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Skeletal muscle perilipin 3 and coatomer proteins are increased following exercise and are associated with fat oxidation.
PLoS ONE
PUBLISHED: 01-01-2014
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Lipid droplet-associated proteins such as perilipin 3 (PLIN3) and coatomer GTPase proteins (GBF1, ARF1, Sec23a, and ARFRP1) are expressed in skeletal muscle but little is known so far as to their regulation of lipolysis. We aimed here to explore the effects of lipolytic stimulation in vitro in primary human myotubes as well as in vivo following an acute exercise bout. In vitro lipolytic stimulation by epinephrine (100 ?M) or by a lipolytic cocktail (30 ?M palmitate, 4 ?M forskolin, and 0.5 ?M ionomycin, PFI) resulted in increases in PLIN3 protein content. Coatomer GTPases such as GBF1, ARF1, Sec23a, and ARFRP1 also increased in response to lipolytic stimuli. Furthermore, a long duration endurance exercise bout (20 males; age 24.0 ± 4.5 y; BMI 23.6 ± 1.8 kg/m(2)) increased PLIN3 protein in human skeletal muscle (p = 0.03) in proportion to ex vivo palmitate oxidation (r = 0.45, p = 0.04) and whole body in vivo fat oxidation (r = 0.52, p = 0.03). Protein content of ARF1 was increased (p = 0.04) while mRNA expression was increased for several other coatomers (GBF1, ARF1, and Sec23a, all p<0.05). These data provide novel observational insight into the possible relationships between lipolysis and PLIN3 along with these coatomoer GTPase proteins in human skeletal muscle.
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Oncostatin M Is Produced in Adipose Tissue and Is Regulated in Conditions of Obesity and Type 2 Diabetes.
J. Clin. Endocrinol. Metab.
PUBLISHED: 12-02-2013
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Context:Adipose tissue is a highly active endocrine organ that secretes many factors that affect other tissues and whole-body metabolism. Adipocytes are responsive to several glycoprotein 130 (gp130) cytokines, some of which have been targeted as potential antiobesity therapeutics.Objective:Oncostatin M (OSM) is a gp130 family member known to inhibit adipocyte differentiation in vitro, but its effects on other adipocyte properties are not characterized. The expression of OSM in white adipose tissue (WAT) has not been evaluated in the context of obesity. Thus, our objective was to examine the expression of adipose tissue OSM in obese animals and humans.Design:OSM expression was examined in adipose tissues from mice with diet-induced and genetic obesity and in obese humans as well as in fractionated adipose tissue from mice. Murine adipocytes were used to examine OSM receptor expression and the effects of OSM on adipocytes, including the secretion of factors such as plasminogen activator inhibitor 1 and IL-6, which are implicated in metabolic diseases.Results:OSM expression is increased in rodent and human obesity/type 2 diabetes mellitus. In humans, OSM levels correlate with body weight and insulin and are inversely correlated with glucose disposal rate as measured by hyperinsulinemic-euglycemic clamp. OSM is not produced from the adipocytes in WAT but derives from cells in the stromovascular fraction, including F4/80(+) macrophages. The specific receptor of OSM, OSM receptor-?, is expressed in adipocytes and adipose tissue and increased in both rodent models of obesity examined. OSM acts on adipocytes to induce the expression and secretion of plasminogen activator inhibitor 1 and IL-6.Conclusions:These data indicate that WAT macrophages are a source of OSM and that OSM levels are significantly induced in murine and human obesity/type 2 diabetes mellitus. These studies suggest that OSM produced from immune cells in WAT acts in a paracrine manner on adipocytes to promote a proinflammatory phenotype in adipose tissue.
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Energy requirements in nonobese men and women: results from CALERIE.
Am. J. Clin. Nutr.
PUBLISHED: 11-20-2013
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The energy intake necessary to maintain weight and body composition is called the energy requirement for weight maintenance and can be determined by using the doubly labeled water (DLW) method.
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An Elevation of Resting Metabolic Rate With Declining Health in Nonagenarians May Be Associated With Decreased Muscle Mass and Function in Women and Men, Respectively.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 10-25-2013
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Previously, we showed that FI34, a frailty index based on 34 health and function ability variables, is heritable and a reliable phenotypic indicator of healthy aging. We have now examined the relationship between major components of energy expenditure and the FI34 in participants of the Louisiana Healthy Aging Study. Resting metabolic rate was associated with FI34, even after adjustment for fat-free mass, fat mass, age, sex, thyroid hormones, and insulin-like growth factor 1 levels, in multiple regression analyses. In contrast, there was no association between total daily energy expenditure and FI34. Circulating creatine phosphokinase, a clinical marker of muscle damage, was also significantly associated with FI34. However, these associations of resting metabolic rate with FI34 were restricted to the oldest old (?90 years) and absent in younger age groups. In oldest old men, the association of FI34 with creatine phosphokinase persisted, whereas in the oldest old women, only the association with resting metabolic rate pertained with the appearance of an effect of body size and composition. These results point toward an increasing metabolic burden for the maintenance of homeodynamics as health declines in nonagenarians, and this has implications for contraction of metabolic reserve that may potentially accelerate the path to disability.
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Fasting plasma adropin concentrations correlate with fat consumption in human females.
Obesity (Silver Spring)
PUBLISHED: 06-20-2013
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This study investigated whether plasma adropin concentrations are influenced by sleep restriction and correlate with dietary preferences.
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Lipid in skeletal muscle myotubes is associated to the donors insulin sensitivity and physical activity phenotypes.
Obesity (Silver Spring)
PUBLISHED: 06-17-2013
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This study investigated the relationship between in vitro lipid content in myotubes and in vivo whole body phenotypes of the donors such as insulin sensitivity, intramyocellular lipids (IMCL), physical activity, and oxidative capacity.
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Adipose tissue expression of Adipose (WDTC1) gene is associated with lower fat mass and enhanced insulin sensitivity in humans.
Obesity (Silver Spring)
PUBLISHED: 06-11-2013
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The overexpression of the adipose gene (adp/WDTC1) in mice inhibits lipid accumulation and improves the metabolic profile. OBJECTIVE: Subcutaneous fat adp expression in humans and its relation to metabolic parameters was evaluated. DESIGN, SETTING, AND METHODS: Abdominal subcutaneous fat adp expression, insulin sensitivity (clamp), and respiratory quotient (RQ; indirect calorimetry) were assessed in: 36 obese and 56 BMI-, race-, and sex-matched type 2 diabetic volunteers (Look AHEAD Adipose Ancillary Study); 37 nondiabetic Pima Indians including obese (n = 18) and nonobese (n = 19) subjects and; 62 nonobese nondiabetic subjects at the Pennington Center in the ADAPT study. RESULTS: In the Look AHEAD Study, adp expression normalized for cyclophilin B was higher in males versus females (1.27 ± 0.06 vs. 1.11 ± 0.04; P < 0.01) but not after controlling for body fat. Adp expression was not influenced by the presence of diabetes but was related to body fat (r = -0.23; P = 0.03), insulin sensitivity (r = 0.23; P = 0.03) and fasting/insulin-stimulated RQ (r = 0.31 and 0.33; P < 0.01). In Pima Indians, adp expression was also higher in males versus females (1.00 ± 0.05 vs. 0.77 ± 0.05; P = 0.02) and higher in nonobese versus obese (1.02 ± 0.05 vs. 0.80 ± 0.06; P = 0.03). In the ADAPT study, there was no difference in adp expression between males and females. CONCLUSION: Consistent with animal studies, our results suggest that high adp expression in human adipose tissue is associated with lower adiposity and enhanced glucose utilization.
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No Effect of Caloric Restriction on Salivary Cortisol Levels in Overweight Men and Women.
Metab. Clin. Exp.
PUBLISHED: 04-19-2013
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The effect of weight loss by diet or diet and exercise on salivary cortisol levels, a measure of hypothalamic pituitary adrenal activity, in overweight individuals is not known. The objective was to test the hypothesis that 24weeks of moderate caloric restriction (CR) (25%) by diet or diet and aerobic exercise would alter morning and diurnal salivary cortisol levels.
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Lateral hypothalamic area deep brain stimulation for refractory obesity: a pilot study with preliminary data on safety, body weight, and energy metabolism.
J. Neurosurg.
PUBLISHED: 04-05-2013
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Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity. The authors present the 2-year safety results as well as early efficacy and metabolic effects in 3 patients undergoing bilateral LHA DBS in the first study of this approach in humans.
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Dynamic model predicting overweight, obesity, and extreme obesity prevalence trends.
Obesity (Silver Spring)
PUBLISHED: 04-01-2013
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Obesity prevalence in the United States appears to be leveling, but the reasons behind the plateau remain unknown. Mechanistic insights can be provided from a mathematical model. The objective of this study is to model known multiple population parameters associated with changes in body mass index (BMI) classes and to establish conditions under which obesity prevalence will plateau.
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Resveratrol vs. calorie restriction: data from rodents to humans.
Exp. Gerontol.
PUBLISHED: 03-19-2013
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Calorie restriction extends lifespan and confers metabolic benefits similar to the effect of lifestyle interventions. Poor compliance to long-term dietary restriction, however, hinders the success of this approach. Evidence is now persuasive for a role of resveratrol supplementation (a polyphenol in red grapes) as potential alternative to calorie restriction. This review summarizes the latest literature on the effects and the molecular mechanisms by which calorie restriction and resveratrol confer health benefits. Resveratrol activates SIRT1 and the associated improvement in energy utilization and insulin sensitivity closely resembles the benefits of calorie restriction. Current data largely support resveratrol as a potential calorie restriction mimetic to improve metabolic and probably functional health. Future studies which characterize the bioavailability and efficacy of resveratrol supplementation are critical to provide evidence for its long-term health benefits.
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Unlocking the barriers to improved functional capacity in the elderly: rationale and design for the "Fit for Life trial".
Contemp Clin Trials
PUBLISHED: 03-01-2013
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Advancing age is associated with an increase in physical impairment, functional limitations, disability, and loss of independence. Regular physical activity conveys health benefits, but the yield on physical function in the elderly, is less clear. Current exercise guidelines are focused predominantly on aerobic programs despite evidence that age-associated declines are mediated by peripheral tissue changes. The Fit for Life trial proposes a new paradigm of exercise training for the elderly that uses a low-mass high-repetition training regimen specifically focused on peripheral tissue beds or body regions (Regional Specific Training Stimulus - RSTS). RSTS is designed to deliver a localized stimulus to the peripheral vasculature, bone and muscle, without imposing a significant central cardiorespiratory strain. The purpose of this study is three-fold; 1) to derive effect sizes from the RSTS intervention by which to power a subsequent larger, confirmatory trial; 2) to assess fidelity of the RSTS intervention; and 3) to assess the interrelationship of the primary endpoints of physical impairment/fitness (VO(2peak), 1 repetition maximal contraction) and function (Senior Fitness Test scores) following two versions of a 4 + 8 week protocol. Men and women over 70 years, at risk for losing independence will be randomized to either 4 weeks of RSTS or "aerobic" exercise, followed by an identical 8 weeks of progressive whole-body training (aerobic plus resistance). The guiding hypothesis is that the magnitude of adaptation after 12 weeks will be greatest in those initially randomized to RSTS. Possible mediators of the intervention effect - physical impairment/fitness and function relationship, including vascular function, muscle mass, strength, and physiology will also be assessed.
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Relationships between body roundness with body fat and visceral adipose tissue emerging from a new geometrical model.
Obesity (Silver Spring)
PUBLISHED: 01-21-2013
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OBJECTIVE: To develop a new geometrical index that combines height, waist circumference (WC), and hip circumference (HC) and relate this index to total and visceral body fat. DESIGN AND METHODS: Subject data were pooled from three databases that contained demographic, anthropometric, dual energy X-ray absorptiometry (DXA) measured fat mass, and magnetic resonance imaging measured visceral adipose tissue (VAT) volume. Two elliptical models of the human body were developed. Body roundness was calculated from the model using a well-established constant arising from the theory. Regression models based on eccentricity and other variables were used to predict %body fat and %VAT. RESULTS: A body roundness index (BRI) was derived to quantify the individual body shape in a height-independent manner. Body roundness slightly improved predictions of %body fat and %VAT compared to the traditional metrics of body mass index (BMI), WC, or HC. On this basis, healthy body roundness ranges were established. An automated graphical program simulating study results was placed at http://www.pbrc.edu/bodyroundness. CONCLUSION: BRI, a new shape measure, is a predictor of %body fat and %VAT and can be applied as a visual tool for health status evaluations.
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Cardiovascular risk escalation with caloric excess: a prospective demonstration of the mechanics in healthy adults.
Cardiovasc Diabetol
PUBLISHED: 01-19-2013
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The link between weight gain and cardiovascular risk characterized with circadian blood pressure variability [CBPV] and endothelial function [EF] is unexplored.
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Determinants of the Changes in Glycemic Control with Exercise Training in Type 2 Diabetes: A Randomized Trial.
PLoS ONE
PUBLISHED: 01-01-2013
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To assess the determinants of exercise training-induced improvements in glucose control (HbA1C) including changes in serum total adiponectin and FFA concentrations, and skeletal muscle peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?) protein content.
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A guide to analysis of mouse energy metabolism.
Nat. Methods
PUBLISHED: 12-28-2011
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We present a consolidated view of the complexity and challenges of designing studies for measurement of energy metabolism in mouse models, including a practical guide to the assessment of energy expenditure, energy intake and body composition and statistical analysis thereof. We hope this guide will facilitate comparisons across studies and minimize spurious interpretations of data. We recommend that division of energy expenditure data by either body weight or lean body weight and that presentation of group effects as histograms should be replaced by plotting individual data and analyzing both group and body-composition effects using analysis of covariance (ANCOVA).
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Approaches for quantifying energy intake and %calorie restriction during calorie restriction interventions in humans: the multicenter CALERIE study.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 11-29-2011
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Calorie restriction (CR) is a component of most weight loss interventions and a potential strategy to slow aging. Accurate determination of energy intake and %CR is critical when interpreting the results of CR interventions; this is most accurately achieved using the doubly labeled water method to quantify total energy expenditure (TEE). However, the costs and analytical requirements of this method preclude its repeated use in many clinical trials. Our aims were to determine 1) the optimal TEE assessment time points for quantifying average energy intake and %CR during long-term CR interventions and 2) the optimal approach for quantifying short-term changes in body energy stores to determine energy intake and %CR during 2-wk DLW periods. Adults randomized to a CR intervention in the multicenter CALERIE study underwent measurements of TEE by doubly labeled water and body composition at baseline and months 1, 3, and 6. Average %CR achieved during the intervention was 24.9 ± 8.7%, which was computed using an approach that included four TEE assessment time points (i.e., TEE(baseline, months 1, 3, and 6)) plus the 6-mo change in body composition. Approaches that included fewer TEE assessments yielded %CR values of 23.4 ± 9.0 (TEE(baseline,) months 3 and 6), 25.0 ± 8.7 (TEE(baseline,) months 1 and 6), and 20.9 ± 7.1% (TEE(baseline, month 6)); the latter approach differed significantly from approach 1 (P < 0.001). TEE declined 9.6 ± 9.9% within 2-4 wk of CR beginning and then stabilized. Regression of daily home weights provided the most reliable estimate of short-term change in energy stores. In summary, optimal quantification of energy intake and %CR during weight loss necessitates a TEE measurement within the first month of CR to capture the rapid reduction in TEE.
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In vivo adipogenesis in rats measured by cell kinetics in adipocytes and plastic-adherent stroma-vascular cells in response to high-fat diet and thiazolidinedione.
Diabetes
PUBLISHED: 11-28-2011
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Impairment of adipogenesis contributes to the development of obesity-related insulin resistance. The current in vitro approaches for its assessment represent crude estimates of the adipogenic potential because of the disruption of the in vivo microenvironment. A novel assessment of in vivo adipogenesis using the incorporation of the stable isotope deuterium ((2)H) into the DNA of isolated adipocytes and stroma-vascular fraction from adipose tissue has been developed. In the current study, we have refined this technique by purifying the adipocytes via a negative immune selection and sorting the plastic adherent stroma-vascular (aSV) subfraction (using 3 h culture) that contains mostly adipocyte progenitor cells and ?10% of small adipocytes. Using a 3-week 8% (2)H(2)O ingestion with a high-fat diet (HFD) or HFD plus pioglitazone (HFD-P), we demonstrate that the fractions of new aSV cells (f(aSV)) and immunopurified adipocytes (f(AD)) (the ratio of their (2)H-enrichment of DNA to the maximal (2)H-enrichment of DNA of bone marrow reference cells) recapitulate the known hyperplastic mechanism of weight gain with pioglitazone treatment. We conclude that f(aSV) and f(AD) are reliable indices of in vivo adipogenesis. The proposed method represents a valuable tool for studying the effect of interventions (drugs, diets, and exercise) on in vivo adipogenesis.
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Ectopic lipid accumulation and reduced glucose tolerance in elderly adults are accompanied by altered skeletal muscle mitochondrial activity.
J. Clin. Endocrinol. Metab.
PUBLISHED: 11-02-2011
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Aging is associated with insulin resistance and unfavorable changes in body composition including increased fat accumulation, particularly in visceral and ectopic depots. Recent studies suggest that skeletal muscle mitochondrial activity may underlie some age-associated metabolic abnormalities.
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Novel strategy for the use of leptin for obesity therapy.
Expert Opin Biol Ther
PUBLISHED: 09-13-2011
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Obesity is a chronic disease and a major global health challenge. Apart from bariatric surgery, which is costly and not without risk, there are currently no successful long-term treatment options for obesity. The history of pharmacological agents for obesity has been turbulent with many examples of drugs being removed from the market due to significant side effects. Orlistat and sibutramine (the latest drugs on the market) provide only modest weight loss and are both associated with high attrition rates due to intolerable side effects. Furthermore, sibutramine was recently withdrawn from the market. There is a need for the development of safe and efficacious drug treatments for obesity.
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Loss of taste responds to high-dose biotin treatment.
J Am Coll Nutr
PUBLISHED: 09-08-2011
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We saw 2 patients who lost their sense of taste, which was restored by pharmacologic doses of biotin. The key objective is to describe the 2 case reports and suggest a potential treatment for unexplained loss of taste.
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Energy balance: an overview with emphasis on children.
Pediatr Blood Cancer
PUBLISHED: 09-06-2011
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Childhood obesity is a significant public health problem, affecting one in five children in the United States. At the crux of this issue is a dysregulation of energy intake and energy expenditure. This review will provide an overview on energy and nutrient balance. We discuss energy balance studies in children using indirect and direct measures, and focus particularly on obesity as a deleterious consequence in childhood survivors of cancer. Obesity affects 11-57% of children with acute lymphoblastic leukemia, probably due to increased energy intake and reduced energy expenditure secondary to reduced habitual activity caused by fatigue. However, most of the studies in children with leukemia are retrospective, use BMI as a measure of obesity, and are inconclusive about the impact of the type of treatment on the development of obesity later in life. To better understand the etiology of obesity in both healthy and sick children, we need to undertake nutrient balance studies with appropriate measures of fat mass and fat distribution while keeping in mind the influence of normal tissue growth and puberty on energy balance.
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Impaired insulin sensitivity and elevated ectopic fat in healthy obese vs. nonobese prepubertal children.
Obesity (Silver Spring)
PUBLISHED: 08-25-2011
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Insulin sensitivity is impaired and ectopic fat (accretion of lipids outside of typical adipose tissue depots) increased in obese adults and adolescents. It is unknown how early in life this occurs; thus, it is important to evaluate young children to identify potential factors leading to the development of metabolic syndrome. We examined an ethnically diverse cohort of healthy, exclusively prepubertal children (N = 123; F = 57, M = 66; age 8.04 ± 0.77 years) to examine differences in insulin sensitivity and ectopic and visceral fat deposition between obese and nonobese youth. Obesity was categorized by age- and sex-adjusted BMI z-scores (nonobese = z-score <2 (N = 94) and obese = z-score ?2 (N = 29)). Insulin sensitivity was assessed by both a frequently sampled intravenous glucose tolerance test (S(i)) and the homeostatic model assessment of insulin resistance (HOMA(IR)). Intramyocellular lipids (IMCLs) from soleus and intrahepatic lipids (IHLs) were assessed by magnetic resonance spectroscopy, visceral adipose tissue (VAT) by magnetic resonance imaging, and total body fat by dual-energy X-ray absorptiometry. We also examined serum lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol) and blood pressure (diastolic and systolic). Obese children exhibited significantly lower S(i) (5.9 ± 5.98 vs. 13.43 ± 8.18 (mµ/l)(-1)·min(-1), P = 0.01) and HDL-C and higher HOMA(IR) (1.68 ± 1.49 vs. 0.63 ± 0.47, P < 0.0001), IMCL (0.74 ± 0.39 vs. 0.44 ± 0.21% water peak, P < 0.0001), IHL (1.49 ± 1.13 vs. 0.54 ± 0.42% water peak, P < 0.0001), VAT (20.16 ± 8.01 vs. 10.62 ± 5.44 cm(2), P < 0.0001), total cholesterol, triglycerides, low-density lipoprotein cholesterol, and systolic blood pressure relative to nonobese children. These results confirm significantly increased ectopic fat and insulin resistance in healthy obese vs. nonobese children prior to puberty. Excessive adiposity during early development appears concomitant with precursors of type 2 diabetes and the metabolic syndrome.
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Brown adipose tissue and aging.
Curr Opin Clin Nutr Metab Care
PUBLISHED: 08-25-2011
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Brown adipose tissue (BAT) was thought to be a tissue with physiological importance early in life (maintenance of body temperature) and to disappear after birth. Recent studies using functional imaging have identified the presence of BAT activity throughout life. This review focuses on the effect of age on BAT function as well as BAT as a potential therapeutic target against age-related metabolic diseases.
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The fall in leptin concentration is a major determinant of the metabolic adaptation induced by caloric restriction independently of the changes in leptin circadian rhythms.
J. Clin. Endocrinol. Metab.
PUBLISHED: 07-21-2011
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Leptin is involved in the hormonal regulation of the reproductive, somatotropic, thyroid, and autonomic axes and ultimately in the regulation of energy balance. In parallel to the metabolic adaptation observed in response to caloric restriction (CR), plasma leptin concentrations are substantially decreased, suggesting a role for this hormone in the drop in energy expenditure beyond that predicted by the changes in body composition (metabolic adaptation).
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Role of skeletal muscle mitochondrial density on exercise-stimulated lipid oxidation.
Obesity (Silver Spring)
PUBLISHED: 06-16-2011
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Reduced skeletal muscle mitochondrial density is proposed to lead to impaired muscle lipid oxidation and increased lipid accumulation in sedentary individuals. We assessed exercise-stimulated lipid oxidation by imposing a prolonged moderate-intensity exercise in men with variable skeletal muscle mitochondrial density as measured by citrate synthase (CS) activity. After a 2-day isoenergetic high-fat diet, lipid oxidation was measured before and during exercise (650 kcal at 50% VO(2)max) in 20 healthy men with either high (HI-CS = 24 ± 1; mean ± s.e.) or low (LO-CS = 17 ± 1 nmol/min/mg protein) muscle CS activity. Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Respiratory exchange data and blood samples were collected at rest and throughout the exercise. HI-CS subjects had higher VO(2)max (50 ± 1 vs. 44 ± 2 ml/kg fat free mass/min; P = 0.01), lower fasting respiratory quotient (RQ) (0.81 ± 0.01 vs. 0.85 ± 0.01; P = 0.04) and higher ex vivo muscle palmitate oxidation (866 ± 168 vs. 482 ± 78 nmol/h/mg muscle; P = 0.05) compared to LO-CS individuals. However, whole-body exercise-stimulated lipid oxidation (20 ± 2 g vs. 19 ± 1 g; P = 0.65) and plasma glucose, lactate, insulin, and catecholamine responses were similar between the two groups. In conclusion, in response to the same energy demand during a moderate prolonged exercise bout, reliance on lipid oxidation was similar in individuals with high and low skeletal muscle mitochondrial density. This data suggests that decreased muscle mitochondrial density may not necessarily impair reliance on lipid oxidation over the course of the day since it was normal under a high-lipid oxidative demand condition. Twenty-four-hour lipid oxidation and its relationship with mitochondrial density need to be assessed.
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Dietary adherence to long-term controlled feeding in a calorie-restriction study in overweight men and women.
Nutr Clin Pract
PUBLISHED: 05-19-2011
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The success of clinical dietary interventions depends on the motivation and willingness of study participants to adhere to the prescribed or provided diet. The aim of this study was to assess participants adherence to their provided diet over the 6-month duration of the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE).
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The implication of brown adipose tissue for humans.
Annu. Rev. Nutr.
PUBLISHED: 05-10-2011
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We here discuss the role of brown adipose tissue on energy homeostasis and assess its potential as a target for body weight management. Because of their high number of mitochondria and the presence of uncoupling protein 1, brown fat adipocytes can be termed as energy inefficient for adenosine-5-triphosphate (ATP) production but energy efficient for heat production. Thus, the energy inefficiency of ATP production, despite high energy substrate oxidation, allows brown adipose tissue to generate heat for body temperature regulation. Whether such thermogenic property also plays a role in body weight regulation is still debated. The recent (re)discovery of brown adipose tissue in human adults and a better understanding of brown adipose tissue development have encouraged the quest for new alternatives to treat obesity since obese individuals seem to have less brown adipose tissue mass/activity than do their lean counterparts. In this review, we discuss the physiological relevance of brown adipose tissue on thermogenesis and its potential usefulness on body weight control in humans.
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Trunk versus extremity adiposity and cardiometabolic risk factors in white and African American adults.
Diabetes Care
PUBLISHED: 04-19-2011
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To determine contributions of trunk and extremity adiposity to cardiometabolic risk factors (blood pressure, fasting blood glucose, HDL cholesterol, and triglycerides) among white and African American adults.
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Development of adherence metrics for caloric restriction interventions.
Clin Trials
PUBLISHED: 03-08-2011
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objective measures are needed to quantify dietary adherence during caloric restriction (CR) while participants are freeliving. One method to monitor adherence is to compare observed weight loss to the expected weight loss during a prescribed level of CR. Normograms (graphs) of expected weight loss can be created from mathematical modeling of weight change to a given level of CR, conditional on the individuals set of baseline characteristics. These normograms can then be used by counselors to help the participant adhere to their caloric target.
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Aerobic exercise in women with polycystic ovary syndrome improves ovarian morphology independent of changes in body composition.
Fertil. Steril.
PUBLISHED: 01-17-2011
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In a prospective study, eight women with polycystic ovary syndrome completed 16 weeks of individualized aerobic exercise training. Independent of changes in body weight and adiposity there was a statistically significant increase in aerobic fitness and insulin sensitivity and a statistically significant decrease in the total number of follicles measured by magnetic resonance imaging.
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The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.
Nat. Med.
PUBLISHED: 01-09-2011
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The emergence of chronic inflammation during obesity in the absence of overt infection or well-defined autoimmune processes is a puzzling phenomenon. The Nod-like receptor (NLR) family of innate immune cell sensors, such as the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (Nlrp3, but also known as Nalp3 or cryopyrin) inflammasome are implicated in recognizing certain nonmicrobial originated danger signals leading to caspase-1 activation and subsequent interleukin-1? (IL-1?) and IL-18 secretion. We show that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity. We further found that the Nlrp3 inflammasome senses lipotoxicity-associated increases in intracellular ceramide to induce caspase-1 cleavage in macrophages and adipose tissue. Ablation of Nlrp3 in mice prevents obesity-induced inflammasome activation in fat depots and liver as well as enhances insulin signaling. Furthermore, elimination of Nlrp3 in obese mice reduces IL-18 and adipose tissue interferon-? (IFN-?) expression, increases naive T cell numbers and reduces effector T cell numbers in adipose tissue. Collectively, these data establish that the Nlrp3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
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Ethnic-specific BMI and waist circumference thresholds.
Obesity (Silver Spring)
PUBLISHED: 01-06-2011
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BMI and waist circumference (WC) are used to identify individuals with elevated obesity-related health risks. The current thresholds were derived largely in populations of European origin. This study determined optimal BMI and WC thresholds for the identification of cardiometabolic risk among white and African-American (AA) adults. The sample included 2096 white women, 1789 AA women, 1948 white men, and 643 AA men aged 18-64 years. Elevated cardiometabolic risk was defined as ?2 risk factors (blood pressure ? 130/85 mm Hg; glucose ?100 mg/dl; triglycerides ?150 mg/dl; high-density lipoprotein-cholesterol <40 mg/dl (men) or <50 mg/dl (women)). Receiver Operating Characteristic (ROC) curves were used to identify optimal BMI and WC thresholds in each sex-by-ethnicity group. The optimal BMI thresholds were 30 kg/m2 in white women, 32.9 kg/m2 in AA women, 29.1 kg/m2 white men, and 30.4 kg/m2 in AA men, whereas optimal WC thresholds were 91.9 cm in white women, 96.8 cm in AA women, 99.4 in white men, and 99.1 cm in AA men. The sensitivities at the optimal thresholds ranged from 63.5 to 68.5% for BMI and 68.4 to 71.0% for WC and the specificities ranged from 64.2 to 68.8% for BMI and from 68.5 to 71.0% for WC, respectively. In general, the optimal BMI and WC thresholds approximated currently used thresholds in men and in white women. There are no apparent ethnic differences in men; however, in AA women the optimal BMI and WC values are ~3 kg/m2 and 5 cm higher than in white women.
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Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure.
J. Clin. Endocrinol. Metab.
PUBLISHED: 12-29-2010
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Lorcaserin, a selective 5-hydroxytryptamine (5-HT)(2C) receptor agonist, reduces body weight. It is unclear whether weight loss is due to reduced energy intake (EI) or also to enhanced energy expenditure (EE).
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Consistency of fat mass--fat-free mass relationship across ethnicity and sex groups.
Br. J. Nutr.
PUBLISHED: 12-14-2010
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The model developed by Forbes (1987) of how body fat mass (FM) and fat-free mass (FFM) change during periods of weight loss or gain (? body weight (BW)) assumed that they change in relationship to a constant C = 10·4, where ?FFM/?BW = 10·4/(10·4+FM). Forbes derived C based on aggregated, cross-sectional data from a small sample of women. The objective of the present study was to reanalyse the relationship described by Forbes and to explore whether this relationship is consistent across ethnicity and sex groups using cross-sectional data from a large sample of white and African-American men and women. Baseline data from white and African-American men and women aged 18-60 years, who participated in a clinical study at the Pennington Biomedical Research Center since 2001 and who underwent dual-energy X-ray absorptiometry scans, were available for analysis. To overcome differences in BMI distributions among the ethnicity-by-sex groups, a stratified random sample of participants was selected within each group such that numbers in each BMI category ( < 25, 25-29·9, 30-34·9, 35-39·9, 40+ kg/m2) were proportional to those within the group with the smallest sample size, yielding a sample of 1953 individuals. Linear regression models assessed the FM-FFM relationship across the four ethnicity-by-sex groups. The FM-FFM relationship varied little by ethnicity (P = 0·57) or by sex (P = 0·26). The constant describing the FM-FFM relationship was estimated to be 9·7 (95 % CI 9·0, 10·3). In conclusion, results from our large, biethnic sample of men and women found a FM-FFM relationship very close to that originally described by Forbes, absent of significant variability by ethnicity or sex.
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Effect of caloric restriction with and without exercise on metabolic intermediates in nonobese men and women.
J. Clin. Endocrinol. Metab.
PUBLISHED: 12-01-2010
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The objective of the study was to evaluate whether serum concentrations of metabolic intermediates are related to adiposity and insulin sensitivity (Si) in overweight healthy subjects and compare changes in metabolic intermediates with similar weight loss achieved by diet only or diet plus exercise.
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Can increased muscle ROS scavenging keep older animals young and metabolically fit?
Cell Metab.
PUBLISHED: 11-27-2010
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Insulin resistance and lipid accumulation occur with aging, perhaps due to mitochondrial dysfunction. In this issue of Cell Metabolism (Lee et al., 2010), older mice overexpressing mitochondrial targeted catalase had reduced muscle mitochondrial oxidative damage, lower intramuscular lipid, and improved insulin sensitivity, suggesting that enhanced ROS scavenging prevents age-associated mitochondrial impairments and insulin resistance.
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The relationship of waist circumference and BMI to visceral, subcutaneous, and total body fat: sex and race differences.
Obesity (Silver Spring)
PUBLISHED: 10-14-2010
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The purpose of this study was to examine sex and race differences in the relationship between anthropometric measurements and adiposity in white and African-American (AA) adults. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured with computed tomography (CT). Fat mass (FM) was measured with dual-energy-X-ray absorptiometry (DXA). Correlation coefficients were used to assess the relationship of waist circumference (WC) and BMI to VAT, SAT, and FM within sex-by-race groups. General linear models were used to compare relationships between WC or BMI, and adiposity across sex and race, within age groups (18-39 and 40-64 years). The sample included 1,667 adults (men: 489 white; 120 AA; women: 666 white, 392 AA). WC and BMI correlations were highest for FM and SAT compared to VAT. Women had higher FM levels than men regardless of WC, but the sex difference in FM was attenuated in younger AA adults with a high BMI. For a given level of WC or BMI, women had higher levels of SAT than men; however, significant interactions indicated that the relationship was not consistent across all levels of BMI and WC. Sex and race differences in VAT varied significantly with WC and BMI. In general, white adults had higher levels of VAT than AA adults at higher levels of BMI and WC. Sex differences, and in some instances race differences, in the relationships between anthropometry and fat-specific depots demonstrate that these characteristics need to be considered when predicting adiposity from WC or BMI.
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Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 10-05-2010
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In a robust and consistent manner, sustained caloric restriction (CR) has been shown to retard the aging process in a variety of animal species. Nonhuman primate studies suggest that CR may have similar effects in longer-lived species. The CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy) research program is the first systematic investigation of CR in nonobese human beings. In the phase 2 study, it is hypothesized that 2 years of sustained CR, involving a 25% reduction of ad libitum energy intake, results in beneficial effects similar to those observed in animal studies. This article presents the design and implementation of this study.
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Effect of dihydrocapsiate on resting metabolic rate in humans.
Am. J. Clin. Nutr.
PUBLISHED: 09-08-2010
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Dihydrocapsiate is a capsinoid found in chili peppers. Dihydrocapsiate is similar to capsaicin, which is known for its thermogenic properties.
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Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes.
Antioxid. Redox Signal.
PUBLISHED: 08-28-2010
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The current societal environment is marked by overabundant accessibility of food coupled with a strong trend of reduced physical activity, both leading to the development of a constellation of disorders, including central obesity, insulin resistance, dyslipidemia, and hypertension (metabolic syndrome). Prolonged calorie restriction (CR) has been shown to extend both the median and maximal lifespan in a variety of lower species such as yeast, worms, fish, rats, and mice. Mechanisms of this CR-mediated lifespan extension are not fully elucidated, but possibly involve significant alterations in energy metabolism, oxidative damage, insulin sensitivity, inflammation, and functional changes in both the neuroendocrine and sympathetic nervous systems. Here we review some of the major physiological, psychological, and behavioral changes after 6 months of CR in overweight otherwise healthy volunteers. Special emphasis is given to the first completed clinical studies that have investigated the effects of controlled, high-quality energy-restricted diets on both biomarkers of longevity and on the development of chronic diseases related to age in humans. With the incremental expansion of research endeavors in the area of energy or caloric restriction, data on the effects of CR in animal models and human subjects are becoming more accessible.
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A single-nucleotide variation in a p53-binding site affects nutrient-sensitive human SIRT1 expression.
Hum. Mol. Genet.
PUBLISHED: 08-06-2010
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The SIRTUIN1 (SIRT1) deacetylase responds to changes in nutrient availability and regulates mammalian physiology and metabolism. Human and mouse SIRT1 are transcriptionally repressed by p53 via p53 response elements in their proximal promoters. Here, we identify a novel p53-binding sequence in the distal human SIRT1 promoter that is required for nutrient-sensitive SIRT1 transcription. In addition, we show that a common single-nucleotide (C/T) variation in this sequence affects nutrient deprivation-induced SIRT1 transcription, and calorie restriction-induced SIRT1 expression. The p53-binding sequence lies in a region of the SIRT1 promoter that also binds the transcriptional repressor Hypermethylated-In-Cancer-1 (HIC1). Nutrient deprivation increases occupancy by p53, while decreasing occupancy by HIC1, of this region of the promoter. HIC1 and p53 compete with each other for promoter occupancy. In comparison with the T variation, the C variation disrupts the mirror image symmetry of the p53-binding sequence, resulting in decreased binding to p53, decreased nutrient sensitivity of the promoter and impaired calorie restriction-stimulated tissue expression of SIRT1 and SIRT1 target genes AMPK?2 and PGC-1?. Thus, a common SNP in a novel p53-binding sequence in the human SIRT1 promoter affects nutrient-sensitive SIRT1 expression, and could have a significant impact on calorie restriction-induced, SIRT1-mediated, changes in human metabolism and physiology.
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HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging.
Aging Cell
PUBLISHED: 08-04-2010
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The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.
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Differences in insulin resistance in Mexican and U.S. Pima Indians with normal glucose tolerance.
J. Clin. Endocrinol. Metab.
PUBLISHED: 07-28-2010
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Insulin resistance is a major risk factor for the development of type 2 diabetes in Pima Indians, a population with the highest prevalence of type 2 diabetes mellitus in the world. Their Mexican counterpart, living a traditional lifestyle in the mountains of Sonora, have at least 5 times less diabetes than the U.S. Pima Indians.
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Obesity in the elderly: is faulty metabolism to blame?
Aging health
PUBLISHED: 06-22-2010
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The fastest growing segment of the US population, and that of other developed countries, is the oldest-old (aged >85 years). Many children born after the year 2000 in countries with the longest lived residents may live to see their 100th birthday. The combination of reduced mortality along with reduced fertility in developed countries is producing population aging, and the comorbidities associated with aging are becoming important public health issues. Age-associated obesity is one such important public health issue. Aging is associated with significant changes in body composition, including loss of skeletal muscle mass and increased visceral fat accumulation. The loss of muscle mass is accompanied by a disproportionate decline in muscle strength (up to three-times greater than the loss of mass), indicative of reduced muscle quality or muscle dysfunctionality. Aging is characterized by markedly reduced physical activity and a drop in resting metabolic rate that is disproportionate to the loss of muscle mass, with a shift towards preferentially oxidizing carbohydrate at the expense of fat. A combination of these factors may act to increase muscular lipid infiltration and decrease insulin sensitivity; however, the cause and effect relationship remains undetermined. Changes in cellular energy (i.e., ATP) requirement owing to decreased ion channel activity, decreased protein synthesis or increased mitochondrial energy efficiency may underlie the decreased resting metabolic rate. Increasing energy demand through physical activity may alleviate some of the adverse metabolic changes that are associated with aging.
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Reduced oxygenation in human obese adipose tissue is associated with impaired insulin suppression of lipolysis.
J. Clin. Endocrinol. Metab.
PUBLISHED: 05-13-2010
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Adipose tissue in obese individuals is characterized by reduced capillary density and reduced oxygenation.
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The presence and role of brown fat in adult humans.
Curr. Diab. Rep.
PUBLISHED: 04-29-2010
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Over the past decade, studies in nuclear medicine using positron-emisson tomography in conjunction with computed tomography (PET/CT) clearly revealed the presence of brown adipose tissue (BAT) in adult humans. Last year, highly publicized papers suggested a potential role for BAT to regulate not only human body temperature but possibly energy balance. Whether BAT can be up regulated in adult humans remain to be shown? Furthermore, the potential role of BAT in the regulation of energy balance needs to be investigated in response to overfeeding.
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Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease PARL.
Cell Metab.
PUBLISHED: 04-07-2010
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Type 2 diabetes mellitus (T2DM) and aging are characterized by insulin resistance and impaired mitochondrial energetics. In lower organisms, remodeling by the protease pcp1 (PARL ortholog) maintains the function and lifecycle of mitochondria. We examined whether variation in PARL protein content is associated with mitochondrial abnormalities and insulin resistance. PARL mRNA and mitochondrial mass were both reduced in elderly subjects and in subjects with T2DM. Muscle knockdown of PARL in mice resulted in malformed mitochondrial cristae, lower mitochondrial content, decreased PGC1alpha protein levels, and impaired insulin signaling. Suppression of PARL protein in healthy myotubes lowered mitochondrial mass and insulin-stimulated glycogen synthesis and increased reactive oxygen species production. We propose that lower PARL expression may contribute to the mitochondrial abnormalities seen in aging and T2DM.
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Urinary C-peptide excretion: a novel alternate measure of insulin sensitivity in physiological conditions.
Obesity (Silver Spring)
PUBLISHED: 04-01-2010
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Insulin sensitivity (IS) is measured by the euglycemic-hyperinsulinemic clamp under a nonphysiological condition. Daily C-peptide urinary excretion may be a physiological index of IS, because C-peptide is co-secreted with insulin as a function of nutrient intake and IS. The amount of (2)H(2)O released from glycolytic glucose metabolism after [6,6-(2)H(2)]-glucose ingestion was recently proposed as a physiological measure of IS. We compared these IS surrogates to the gold standard (euglycemic-hyperinsulinemic clamp). Thirty (15 male/15 female) sedentary, nondiabetic participants (27.2 +/- 4.0 (s.d.) kg/m(2), 35 +/- 12 years) were admitted for 3 days to our in-patient unit. After a 10-h fast, they received 60 g of glucose and 15 g of [6,6-(2)H(2)]-glucose. Before glucose ingestion and hourly thereafter for 4 h, plasma glucose and insulin concentrations, and plasma deuterium enrichment were determined. Plasma (2)H(2)O production divided by insulin response was used as the glycolytic index. On day 2, subjects spent 23 h in a metabolic chamber (eucaloric diet, 50% carbohydrate, 30% fat). Urinary C-peptide excretion was divided by energy intake yielding the C-peptide to energy intake ratio (CPEP/EI). After leaving the chamber (day 3, 10-h fast), IS was measured by a 2-h clamp (120 mU/m(2)/min). Average IS (clamp) was 7.3 +/- 2.6 mg glucose/kg estimated metabolic body size/min (range: 3.6-13.2). These values were inversely correlated with CPEP/EI (r = -0.62; P < 0.01) and positively with the glycolytic rate (r = 0.60; P < 0.01). In nondiabetic subjects, two novel estimates of IS--daily urinary C-peptide urinary excretion and glycolytic rate during an oral glucose tolerance test --were related to IS by a clamp.
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Development of a serum profile for healthy aging.
Age (Dordr)
PUBLISHED: 01-25-2010
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Increasing numbers of Americans are reaching 85 years of age or older, yet there are no reliable biomarkers to predict who will live this long. The goal of this pilot study therefore was: (1) to identify a potential serum pattern that could identify proteins involved in longevity and (2) to determine if this pattern was a marker of longevity in an independent sample of individuals. Serum samples were analyzed in three cohorts of individuals (n = 12 in each) aged 20-34, 60-74, and ? 90 years who participated in The Louisiana Healthy Aging Study. The 12 most abundant proteins were removed and the remaining proteins separated by two-dimensional gel electrophoresis. Gels were matched and the intensity of each spot quantified. Multivariate discriminant analysis was used to identify a serum pattern that could separate these three age cohorts. Seven protein spots were found that correctly distinguished the subjects into the three groups. However, these spots were not as successful in discriminating the ages in a second set of 15 individuals as only eight of these subjects were placed into their correct group. These preliminary results show that the proteomics approach can be used to identify potential proteins or markers that may be involved in the aging process and/or be important determinants of longevity.
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Leptin replacement prevents weight loss-induced metabolic adaptation in congenital leptin-deficient patients.
J. Clin. Endocrinol. Metab.
PUBLISHED: 01-08-2010
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Context: Leptin regulates energy homeostasis by suppressing food intake; however, its role in energy expenditure and fat oxidation remains uncertain in humans. Objective: The aim of the study was to assess 24-h energy metabolism before and after weight loss induced by leptin treatment in congenital leptin-deficient subjects or low-calorie diet in controls. Design and Patients: We measured 24-h energy expenditure, 24-h fat oxidation, and body fat in three null homozygous leptin-deficient obese adults before and after weight loss induced by a 19-wk leptin replacement period (0.02-0.04 mg/kg/d). The same measures were performed in three obese controls pair-matched for sex, age, and weight loss induced by a 10- to 21-wk low-calorie diet. Measurements were preceded for 1 wk of weight stabilization. Energy expenditure was adjusted for fat-free mass, fat mass, sex, and age based on a reference population (n = 842; R(2) = 0.85; P < 0.0001). Similarly, fat oxidation was adjusted for fat-free mass, percentage body fat, energy balance, and diet composition during the 24-h respiratory chamber stay (R(2) = 0.38; P < 0.0001). Results: Before weight loss, congenital leptin-deficient and control subjects had similar energy expenditure. However, after weight loss ( approximately 15 kg), controls had energy expenditures lower than expected for their new weight and body composition (-265 +/- 76 kcal/d; P = 0.04), whereas leptin-treated subjects had values not different from the reference population (-128 +/- 119 kcal/d; P = 0.67). Before weight loss, fat oxidation was similar between groups. However, after weight loss, leptin-treated subjects had higher fat oxidation than controls (P = 0.005) and higher than the reference population (P = 0.0001). Conclusion: In congenital leptin-deficient subjects, leptin replacement prevented the decrease in energy expenditure and fat oxidation often observed after weight loss.
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Metabolic changes following a 1-year diet and exercise intervention in patients with type 2 diabetes.
Diabetes
PUBLISHED: 12-22-2009
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To characterize the relationships among long-term improvements in peripheral insulin sensitivity (glucose disposal rate [GDR]), fasting glucose, and free fatty acids (FFAs) and concomitant changes in weight and adipose tissue mass and distribution induced by lifestyle intervention in obese individuals with type 2 diabetes.
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Ghrelin and peptide YY in postpartum lactating and nonlactating women.
Am. J. Clin. Nutr.
PUBLISHED: 12-09-2009
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Epidemiologic studies suggest that childbearing is an important contributor to the development of obesity in many women and that breastfeeding may be protective. Ghrelin and peptide YY (PYY) are gut hormones involved in appetite regulation and energy homeostasis and are biological neuroendocrine signals that potentially affect body weight and adiposity.
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Effects of endurance running and dietary fat on circulating ghrelin and peptide YY.
J Sports Sci Med
PUBLISHED: 12-01-2009
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Ghrelin and peptide YY (PYY) are newly recognized gut peptides involved in appetite regulation. Plasma ghrelin concentrations are elevated in fasting and suppressed following a meal, while PYY concentrations are suppressed in fasting and elevated postprandially. We determine whether ghrelin and PYY are altered by a low-fat, high-carbohydrate (10% fat, 75% carbohydrate) or moderate-fat, moderate-carbohydrate (35% fat, 50% carbohydrate) diet and; whether these peptides are affected by intense endurance running (which is likely to temporarily suppress appetite). Twenty-one endurance-trained runners followed a controlled diet (25% fat) and training regimen for 3 days before consuming the low-fat or isoenergetic moderate-fat diet for another 3 days in random cross-over fashion. On day 7 runners underwent glycogen restoration and then completed a 90-minute pre-loaded 10-km time trial on day 8, following a control breakfast. Blood samples were obtained on days 4 and 7 (fasting), and day 8 (non-fasting) before and after exercise for analysis of ghrelin, PYY, insulin and growth hormone (GH). Insulin, GH, Ghrelin and PYY changed significantly over time (p < 0.0001) but were not influenced by diet. Ghrelin was elevated during fasting (days 4 and 7), while insulin and PYY were suppressed. Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7). Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001) increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression. These peptides do not appear to be influenced by dietary fat intake.
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Impact of 6-month caloric restriction on autonomic nervous system activity in healthy, overweight, individuals.
Obesity (Silver Spring)
PUBLISHED: 11-12-2009
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Caloric restriction (CR) increases maximum lifespan but the mechanisms are unclear. Dominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PNS) has been shown to be a strong risk factor for cardiovascular disease. Obesity and aging are associated with increased SNS activity, and weight loss and/or exercise seem to have positive effects on this balance. We therefore evaluated the effect of different approaches of CR on autonomic function in 28 overweight individuals participating in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial. Participants were randomized to either control, CR: 25% decrease in energy intake, CREX: 12.5% CR + 12.5% increase in energy expenditure, or LCD: low-calorie diet until 15% weight reduction followed by weight maintenance. Autonomic function was assessed by spectral analysis of heart-rate variability (HRV) while fasting and after a meal. Measurements were performed at baseline and 6 months. HR and SNS index decreased and PNS index increased in all intervention groups but reached significance only in CREX. HR and SNS index increased and PNS index decreased in response to the meal in all intervention groups. The results therefore suggest that weight loss improved SNS/PNS balance especially when CR is combined with exercise.
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The effect of caloric restriction interventions on growth hormone secretion in nonobese men and women.
Aging Cell
PUBLISHED: 10-30-2009
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Lifespan in rodents is prolonged by caloric restriction (CR) and by mutations affecting the somatotropic axis. It is not known if CR can alter the age-associated decline in growth hormone (GH), insulin-like growth factor (IGF)-1 and GH secretion. To evaluate the effect of CR on GH secretory dynamics; forty-three young (36.8 +/- 1.0 years), overweight (BMI 27.8 +/- 0.7) men (n = 20) and women (n = 23) were randomized into four groups; control = 100% of energy requirements; CR = 25% caloric restriction; CR + EX = 12.5% CR + 12.5% increase in energy expenditure by structured exercise; LCD = low calorie diet until 15% weight reduction followed by weight maintenance. At baseline and after 6 months, body composition (DXA), abdominal visceral fat (CT) 11 h GH secretion (blood sampling every 10 min for 11 h; 21:00-08:00 hours) and deconvolution analysis were measured. After 6 months, weight (control: -1 +/- 1%, CR: -10 +/- 1%, CR + EX: -10 +/- 1%, LCD: -14 +/- 1%), fat mass (control: -2 +/- 3%, CR: -24 +/- 3%, CR + EX: -25 +/- 3%, LCD: -31 +/- 2%) and visceral fat (control: -2 +/- 4%, CR: -28 +/- 4%, CR + EX: -27 +/- 3%, LCD: -36 +/- 2%) were significantly (P < 0.001) reduced in the three intervention groups compared to control. Mean 11 h GH concentrations were not changed in CR or control but increased in CR + EX (P < 0.0001) and LCD (P < 0.0001) because of increased secretory burst mass (CR + EX: 34 +/- 13%, LCD: 27 +/- 22%, P < 0.05) and amplitude (CR + EX: 34 +/- 14%, LCD: 30 +/- 20%, P < 0.05) but not to changes in secretory burst frequency or GH half-life. Fasting ghrelin was significantly increased from baseline in all three intervention groups; however, total IGF-1 concentrations were increased only in CR + EX (10 +/- 7%, P < 0.05) and LCD (19 +/- 4%, P < 0.001). A 25% CR diet for 6 months does not change GH, GH secretion or IGF-1 in nonobese men and women.
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Adipose tissue collagen VI in obesity.
J. Clin. Endocrinol. Metab.
PUBLISHED: 10-16-2009
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Basic science studies show that the extracellular matrix of adipose tissue, mainly represented by collagen VI, is dysfunctional in obesity and contributes to the development of the metabolic syndrome. We hypothesized in humans that increased collagen VI alpha3-subunit (COL6A3) mRNA is associated with adipose tissue macrophage chemotaxis and inflammation and that weight gain is accompanied by changes in the expression of COL6A3.
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Racial differences in abdominal depot-specific adiposity in white and African American adults.
Am. J. Clin. Nutr.
PUBLISHED: 10-14-2009
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There is increasing interest in understanding racial differences in adiposity in specific body depots as a way to explain differential health risks associated with obesity.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.