Search

The effects of testosterone on energy and substrate metabolism during energy deficit is unknown. The objective of this study was to determine the effects of weekly testosterone enanthate (TEST; 200 mg/wk) injections on energy expenditure, energy substrate oxidation, and related gene expression during 28 days of energy deficit compared to placebo (PLA).After a 14-day energy balance phase, healthy men were randomly assigned to TEST (n = 24) or PLA (n = 26) for a 28-day controlled diet- and exercise-induced energy deficit (55% below total energy needs by reducing energy intake and increasing physical activity). Whole-room indirect calorimetry and 24-hour urine collections were used to measure energy expenditure and energy substrate oxidation during balance and deficit. Transcriptional regulation of energy and substrate metabolism was assessed using RT-qPCR from rested/fasted muscle biopsy samples collected during balance and deficit.Per protocol design 24-hour energy expenditure increased (P0.05) and energy intake decreased (P0.05) in TEST and PLA during deficit compared to balance. Carbohydrate oxidation decreased (P0.05), while protein and fat oxidation increased (P0.05) in TEST and PLA during deficit compared to balance. Change (∆, deficit minus balance) in 24-hour energy expenditure was associated with ∆activity factor (r = 0.595), but not ∆fat-free mass (r = 0.147). Energy sensing (PRKAB1 and TP53), mitochondria (TFAM and COXIV), fatty acid metabolism (CD36/FAT, FABP, CPT1b, and ACOX1) and storage (FASN), and amino acid metabolism (BCAT2 and BCKHDA) genes were increased (P0.05) during deficit compared to balance, independent of treatment.These data demonstrate that increased physical activity and not exogenous testosterone administration is the primary determinate of whole-body and skeletal muscle metabolic adaptations during diet- and exercise-induced energy deficit.

Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at ~1 yr, declines slowly throughout childhood and adolescence (1-20 yr) to adult levels at ~20 yr, remains stable in adulthood (20-60 yr) even during pregnancy, and declines in older adults (60+ yr). These changes in total expenditure shed new light on human development and aging and should help shape nutrition and health strategies across the lifespan.

Objective This analysis aimed to measure the intraparticipant reliability-the intraclass correlation coefficient-of all the components of daily energy expenditure (EE) (24-hour EE, sleep EE, resting EE, basal EE, and thermic effect of food) over a period of 3 consecutive days in 35 study participants. Methods The components of daily EE and substrate use (respiratory exchange ratio) were measured over 3 consecutive days before and after a 3-week 1,000-kcal/d caloric restriction/weight-loss intervention. Results There was a high degree of reliability for sleep EE (96.8%), 24-hour EE (97.8%), basal EE (90.6%), and resting EE (93.2%) during the run-in period. The intraclass correlation coefficient for the follow-up period after weight loss (3.67 ± 1.10 kg) remained high for sleep EE (95.6%), 24-hour EE (100%), basal EE (96.1%), and resting EE (92.5%). The minimal detectable differences in EE were reduced by 30% for both 24-hour EE and sleep EE when comparing 2 days versus 1 day spent in the whole-room indirect calorimeter. Conclusions The reliability of the daily components of EE is very high both prior to and after a weight-loss intervention. We here provide instrumental data for investigators to adequately power studies investigating energy metabolism using whole-room indirect calorimetry.

Caloric restriction (CR) is a strategy that attenuates aging in multiple nonhuman species. The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trials are part of a research program aiming to test the effects of CR on aging and longevity biomarkers in humans. Building on CALERIE phase 1, CALERIE phase 2 (CALERIE 2) was the largest study to date to assess sustained CR in healthy humans without obesity. In a 24-month randomized controlled trial comprising 218 participants at baseline, CALERIE 2 showed that moderate CR, 11.9% on average, induced improvements in aging-related biomarkers without adversely affecting psychological or behavioral outcomes. The objectives of this report are to summarize and review the highlights of CALERIE 2 and report previously unpublished results on eating disorder symptoms and cognitive function. This article specifically summarizes the physiological, psychological, aging, behavioral, and safety results of the trial. Also provided are research directions beyond CALERIE 2 that highlight important opportunities to investigate the role of CR in aging, longevity, and health span in humans.

PURPOSE: Calorie restriction (CR) is an effective treatment for obesity-related liver and metabolic disease. However, CR studies in individuals without obesity are needed to see if CR could delay disease onset. Liver biomarkers indicate hepatic health and are linked to cardiometabolic disease. Our aim was to examine the effects of a two-year CR intervention on liver biomarkers in healthy individuals without obesity. METHODS: The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study was a two-year randomized controlled trial. Overall, 218 participants (body mass index: 25.1±1.7 kg/m(2)) were enrolled into control group (n=75) that ate ad libitum (AL) or a CR group (n=143) that aimed to decrease energy intake by 25%. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin were measured during the trial. RESULTS: At month 24, relative to the AL group, ALP (−7±1 IU/L; P0.99) or AST (2±2 IU/L; P=0.68) were revealed. However, sex-by-treatment-by-time interactions (P

Purpose of review The prevalence and burden of obesity has reached alarming levels. The assessment of human energy expenditure enables the identification of obesity-prone and obesity-resistant individuals and helps to explain the short and long-term success of weight loss treatments. In this review, we describe the state-of-the-art methods used in the assessment of human energy expenditure and the impact of dietary intake on the interpretation of the data. Recent findings The reference techniques to assess energy expenditure in humans have not significantly changed during the last century. Today, indirect calorimetry, either using a metabolic chamber or a metabolic cart, is the favored method to assess human energy expenditure and is the only method enabling the assessment of macronutrient oxidation. The doubly labeled water method however provides accurate assessment of human energy expenditure under free living conditions. Summary Although energy expenditure and macronutrient oxidation can be assessed by simple calculations from oxygen consumption and carbon dioxide production, these calculations can provide erroneous results or require corrections and/or more complex interpretation when several biochemical pathways are simultaneously engaged. Such physiological mechanisms are often elicited by dietary interventions including, among other, gluconeogenesis, lipogenesis, ketogenesis, alcohol oxidation and under or overfeeding.

Background Type 2 resistant starch (RS2) has been shown to improve metabolic health outcomes and may increase satiety and suppress appetite and food intake in humans. Objective This study assessed whether 12 weeks of daily RS2 supplementation could influence appetite perception, food intake, and appetite-related gut hormones in adults with prediabetes, relative to the control (CTL) group. Design The study was a randomized controlled trial and analysis of secondary study end points. Participants/setting Sixty-eight adults (body mass index ≥27) aged 35 to 75 years with prediabetes were enrolled in the study at Pennington Biomedical Research Center (2012 to 2016). Fifty-nine subjects were included in the analysis. Intervention Participants were randomized to consume 45 g/day of high-amylose maize (RS2) or an isocaloric amount of the rapidly digestible starch amylopectin (CTL) for 12 weeks. Main outcome measures Subjective appetite measures were assessed via visual analogue scale and the Eating Inventory; appetite-related gut hormones (glucagon-like peptide 1, peptide YY, and ghrelin) were measured during a standard mixed-meal test; and energy and macronutrient intake were assessed by a laboratory food intake (buffet) test, the Remote Food Photography Method, and SmartIntake app. Statistical analyses performed Data were analyzed using linear mixed models, adjusting for treatment group and time as fixed effects, with a significance level of α=.05. Results RS2 had no effect on subjective measures of appetite, as assessed by visual analogue scale (P>0.05) and the Eating Inventory (P≥0.24), relative to the CTL group. There were no effects of RS2 supplementation on appetite-related gut hormones, including glucagon-like peptide 1 (P=0.61), peptide YY (P=0.34), and both total (P=0.26) and active (P=0.47) ghrelin compared with the CTL. RS2 had no effect on total energy (P=0.30), carbohydrate (P=0.11), protein (P=0.64), or fat (P=0.37) consumption in response to a buffet meal test, relative to the CTL. In addition, total energy (P=0.40), carbohydrate (P=0.15), protein (P=0.46), and fat (P=0.53) intake, as quantified by the Remote Food Photography Method, were also unaffected by RS2, relative to the CTL. Conclusions RS2 supplementation did not increase satiety or reduce appetite and food intake in adults with prediabetes.

Context This study was designed to understand causes and critical periods for postpartum weight retention by characterizing changes in body composition, energy intake, energy expenditure and physical activity in women with obesity during pregnancy and postpartum. Design In this prospective, observational cohort study, body composition (plethysmography), energy expenditure (doubly labeled water, whole-body room calorimetry), physical activity (accelerometry), metabolic biomarkers, and eating behaviors were measured. Energy intake was calculated by the intake-balance method for pregnancy, and for 2 postpartum periods (0 to 6 months and 6 to 12 months). Results During the 18-month observation period, weight loss occurred in 16 (43%) women (mean ± SEM, −4.9 ± 1.6 kg) and weight retention occurred in 21 (57%) women (+8.6 ± 1.4 kg). Comparing women with postpartum weight loss and weight retention, changes in body weight were not different during pregnancy (6.9 ± 1.0 vs 9.5 ± 0.9 kg, P = 0.06). After pregnancy, women with postpartum weight loss lost −3.6 ± 1.8 kg fat mass whereas women with weight retention gained 6.2 ± 1.7 kg fat mass (P < 0.001). Women with postpartum weight loss reduced energy intake during the postpartum period (compared with during pregnancy) by 300 kcal/d (1255 kJ/d), while women with weight retention increased energy intake by 250 kcal/d (1046 kJ/d, P < 0.005). There were no differences in the duration of breastfeeding, eating behavior, or metabolic biomarkers. Conclusions Postpartum weight gain was the result of increased energy intake after pregnancy rather than decreased energy expenditure. Dietary intake recommendations are needed for women with obesity during the postpartum period, and women should be educated on the risk of overeating after pregnancy.

Current dietary guidelines advocate more plant-based, sustainable diets on the basis of scientific evidence about diet-health relations but also to address environmental concerns. Here, we critically review the effects of plant-based diets on the prevalence of obesity and other health outcomes. Plant-based diets per se have limited efficacy for the prevention and treatment of obesity, but most have beneficial effects in terms of chronic disease risk. However, with the considerable possibilities of translating plant-based diets into various types of dietary patterns, our analysis suggests that potential adverse health effects should also be considered in relation to vulnerable groups of the population. A transition to more plant-based diets may exert beneficial effects on the environment, but is unlikely to affect obesity, and may also have adverse health effects if this change is made without careful consideration of the nutritional needs of the individual relative to the adequacy of the dietary intake.

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction. (C) 2022 The Author(s). Published by Elsevier Ltd.

A recent Perspective article described the “carbohydrate-insulin model (CIM)” of obesity, asserting that it “better reflects knowledge on the biology of weight control” as compared with what was described as the “dominant energy balance model (EBM),” which fails to consider “biological mechanisms that promote weight gain.” Unfortunately, the Perspective conflated and confused the principle of energy balance, a law of physics that is agnostic as to obesity mechanisms, with the EBM as a theoretical model of obesity that is firmly based on biology. In doing so, the authors presented a false choice between the CIM and a caricature of the EBM that does not reflect modern obesity science. Here, we present a more accurate description of the EBM where the brain is the primary organ responsible for body weight regulation operating mainly below our conscious awareness via complex endocrine, metabolic, and nervous system signals to control food intake in response to the body's dynamic energy needs as well as environmental influences. We also describe the recent history of the CIM and show how the latest “most comprehensive formulation” abandons a formerly central feature that required fat accumulation in adipose tissue to be the primary driver of positive energy balance. As such, the new CIM can be considered a special case of the more comprehensive EBM but with a narrower focus on diets high in glycemic load as the primary factor responsible for common obesity. We review data from a wide variety of studies that address the validity of each model and demonstrate that the EBM is a more robust theory of obesity than the CIM.

New appetite-regulating antiobesity treatments such as semaglutide and agents under investigation such as tirzepatide show promise in achieving weight loss of 15% or more. Energy expenditure, fat oxidation, and lean mass preservation are important determinants of weight loss and weight-loss maintenance beyond appetite regulation. This review discusses prior failures in clinical development of weight-loss drugs targeting energy expenditure and explores novel strategies for targeting energy expenditure: mitochondrial proton leak, uncoupling, dynamics, and biogenesis; futile calcium and substrate cycling; leptin for weight maintenance; increased sympathetic nervous system activity; and browning of white fat. Relevant targets for preserving lean mass are also reviewed: growth hormone, activin type II receptor inhibition, and urocortin 2 and 3. We endorse moderate modulation of energy expenditure and preservation of lean mass in combination with efficient appetite reduction as a means of obtaining a significant, safe, and long-lasting weight loss. Furthermore, we suggest that the regulatory guidelines should be revisited to focus more on the quality of weight loss and its maintenance rather than the absolute weight loss. Commitment to this research focus both from a scientific and from a regulatory point of view could signal the beginning of the next era in obesity therapies.

The risk of chronic diseases caused by aging is reduced by caloric restriction (CR)-induced immunometabolic adaptation. Here, we found that the matricellular protein, secreted protein acidic and rich in cysteine (SPARC), was inhibited by 2 years of 14% sustained CR in humans and elevated by obesity. SPARC converted anti-inflammatory macrophages into a pro-inflammatory phenotype with induction of interferon-stimulated gene (ISG) expression via the transcription factors IRF3/7. Mechanistically, SPARC-induced ISGs were dependent on toll-like receptor-4 (TLR4)-mediated TBK1, IRF3, IFN-β, and STAT1 signaling without engaging the Myd88 pathway. Metabolically, SPARC dampened mitochondrial respiration, and inhibition of glycolysis abrogated ISG induction by SPARC in macrophages. Furthermore, the N-terminal acidic domain of SPARC was required for ISG induction, while adipocyte-specific deletion of SPARC reduced inflammation and extended health span during aging. Collectively, SPARC, a CR-mimetic adipokine, is an immunometabolic checkpoint of inflammation and interferon response that may be targeted to delay age-related metabolic and functional decline.

Obesity, insulin resistance, and type 2 diabetes contribute to increased morbidity and mortality in humans. The db/db mouse is an important mouse model that displays many key features of the human disease. Herein, we used the drug pioglitazone, a thiazolidinedione with insulin-sensitizing properties, to investigate blood glucose levels, indicators of islet β-cell health and maturity, and gene expression in adipose tissue. Oral administration of pioglitazone lowered blood glucose levels in db/db mice with a corresponding increase in respiratory quotient, which indicates improved whole-body carbohydrate utilization. In addition, white adipose tissue from db/db mice and from humans treated with pioglitazone showed increased expression of glycerol kinase. Both db/db mice and humans given pioglitazone displayed increased expression of UCP-1, a marker typically associated with brown adipose tissue. Moreover, pancreatic β-cells from db/db mice treated with pioglitazone had greater expression of insulin and Nkx6.1 as well as reduced abundance of the de-differentiation marker Aldh1a3. Collectively, these findings indicate that four weeks of pioglitazone therapy improved overall metabolic health in db/db mice. Our data are consistent with published reports of human subjects administered pioglitazone and with analysis of human adipose tissue taken from subjects treated with pioglitazone. In conclusion, the current study provides evidence that pioglitazone restores key markers of metabolic health and also showcases the utility of the db/db mouse to understand mechanisms associated with human metabolic disease and interventions that provide therapeutic benefit.

Background A metabolic adaptation, defined as an increase in energy expenditure (EE) beyond what is expected with weight gain during overfeeding (OF), has been reported but also refuted. Much of the inconsistency stems from the difficulty in conducting large, well-controlled OF studies in humans. Objectives The primary aim of this study was to determine whether a metabolic adaptation to OF exists and if so, attenuates weight gain. Methods Thirty-five young adults consumed 40% above their baseline energy requirements for 8 wk, and sleeping metabolic rate (SMR) and 24-h sedentary energy expenditure (24h-EE) were measured before and after OF. Subjects were asked to return for a 6-mo post-OF follow-up visit to measure body weight, body composition, and physical activity. Results After adjusting for gains in fat-free mass and fat mass, SMR increased by 43 ± 123 kcal/d more than expected (P = 0.05) and 24h-EE by 23 ± 139 kcal/d (P = 0.34), indicating an overall lack of metabolic adaptation during OF despite a wide variability in the response. Among the 30 subjects who returned for the 6-mo follow-up visit, those who had a lower-than-predicted SMR (basal EE) retained more of the fat gained during OF. Likewise, subjects displaying a higher-than-predicted sedentary 24h-EE lost significantly more fat during the 6-mo follow-up. Conclusions Metabolic adaptation to OF was on average very small but variable between subjects, revealing "thrifty" or "spendthrift" metabolic phenotypes related to body weight loss 6 mo later. This trial was registered at clinicaltrials.gov as NCT01672632.

We previously showed that nightly exposure to moderate hypoxia reduces fasting glucose levels and improves both whole-body skeletal muscle and hepatic insulin sensitivity in individuals with obesity. The goal of this study was to extend this observation in an “at home” setting and determine if nightly exposure to moderate hypoxia improves glucose tolerance in individuals with type 2 diabetes. Eight adults, ages 20–65 years with type 2 diabetes enrolled in our study and slept for 14 consecutive nights at home in a hypoxic tent maintained at 15% O(2) (~2400 m). The primary endpoint was insulin sensitivity (Matsuda Index) calculated from a 75-g oral glucose tolerance test. Secondary endpoints included calculations of insulin secretion and beta-cell function, including the area-under-the-curve (AUC) for glucose and insulin, the Insulinogenic Index, and the Disposition Index. We observed the Matsuda Index trended towards a 29% increase following 14 nights of moderate hypoxia (from 1.7 ± 0.7 to 2.2 ± 1.7; p = 0.06). Two-hour glucose AUC was significantly reduced from 501 ± 99 to 439 ± 65 mg/dL × h (p = 0.01). We conclude that 14 nights of moderate hypoxia improves glucose tolerance in individuals with type 2 diabetes. Future studies should confirm whether exposure to moderate hypoxia consistently improves glucose homeostasis in larger sample sizes.

Objective The objective of this study was to measure changes in glucose, lipid, and inflammation parameters after transitioning from a baseline diet (BD) to an isocaloric ketogenic diet (KD). Methods Glucose homeostasis, lipid homeostasis, and inflammation were studied in 17 men (BMI: 25-35 kg/m2 ) during 4 weeks of a BD (15% protein, 50% carbohydrate, 35% fat) followed by 4 weeks of an isocaloric KD (15% protein, 5% carbohydrate, 80% fat). Postprandial responses were assessed following mixed-meal tests matched to compositions of the BD (control meal [CM]) and KD (ketogenic meal). Results Fasting ketones, glycerol, free fatty acids, glucagon, adiponectin, gastric inhibitory peptide, total and low-density lipoprotein cholesterol, and C-reactive protein were significantly increased on the KD. Fasting insulin, C-peptides, triglycerides, and fibroblast growth factor 21 were significantly decreased. During the KD, the glucose area under the curve was significantly higher with both test meals, and the insulin area under the curve was significantly higher only for the CM. Analyses of glucose homeostasis suggested that the KD insulin sensitivity decreased during the CM but increased during the ketogenic meal. Insulin-mediated antilipolysis was decreased on the KD regardless of meal type. Conclusions Switching to the KD was associated with increased cholesterol and inflammatory markers, decreased triglycerides, and decreased insulin-mediated antilipolysis. Glucose homeostasis parameters were diet dependent and test meal dependent.

BACKGROUND: Low-carbohydrate diets have been reported to significantly increase human energy expenditure when measured using doubly labeled water (DLW) but not by respiratory chambers. Although DLW may reveal true physiological differences undetected by respiratory chambers, an alternative possibility is that the expenditure differences resulted from failure to correctly estimate the respiratory quotient (RQ) used in the DLW calculations. OBJECTIVE: To examine energy expenditure differences between isocaloric diets varying widely in carbohydrate and to quantitatively compare DLW data with respiratory chamber and body composition measurements within an energy balance framework. DESIGN: DLW measurements were obtained during the final 2 wk of month-long baseline (BD; 50% carbohydrate, 35% fat, 15% protein) and isocaloric ketogenic diets (KD; 5% carbohydrate, 80% fat, 15% protein) in 17 men with a BMI of 25–35 kg/m(2). Subjects resided 2 d/wk in respiratory chambers to measure energy expenditure (EE(chamber)). DLW expenditure was calculated using chamber-determined RQ either unadjusted (EE(DLW)) or adjusted (EE(DLWΔRQ)) for net energy imbalance using diet-specific coefficients. Accelerometers measured physical activity. Body composition changes were measured by dual-energy X-ray absorptiometry (DXA) which were combined with energy intake measurements to calculate energy expenditure by balance (EE(bal)). RESULTS: After transitioning from BD to KD, neither EE(chamber) nor EE(bal) were significantly changed (∆EE(chamber )= 24 ± 30 kcal/d; P = 0.43 and ∆EE(bal )= −141 ± 118 kcal/d; P = 0.25). Similarly, physical activity (−5.1 ± 4.8%; P = 0.3) and exercise efficiency (−1.6 ± 2.4%; P = 0.52) were not significantly changed. However, EE(DLW) was 209 ± 83 kcal/d higher during the KD (P = 0.023) but was not significantly increased when adjusted for energy balance (EE(DLWΔRQ) = 139 ± 89 kcal/d; P = 0.14). After removing 2 outliers whose EE(DLW) were incompatible with other data, EE(DLW) was marginally increased during the KD by 126 ± 62 kcal/d (P = 0.063) and EE(DLW∆RQ) was only 46 ± 65 kcal/d higher (P = 0.49). CONCLUSIONS: DLW calculations failing to account for diet-specific energy imbalance effects on RQ erroneously suggest that low-carbohydrate diets substantially increase energy expenditure. This trial was registered at clinicaltrials.gov as NCT01967563.

BACKGROUND & AIMS: Indirect comparisons suggest that alternate-day fasting (ADF) may produce greater improvements in body composition, fat distribution, and/or the adipokine profile compared to daily calorie restriction (CR), but this has not been tested directly. In a pre-planned secondary analysis of a randomized controlled trial, we compared changes in the VAT:SAT ratio, FFM:total mass ratio, and the adipokine profile between ADF and CR. METHODS: Overweight and obese participants (n = 100) were randomized to 1) ADF (alternating every 24-h between consuming 25% or 125% of energy needs); 2) CR (consuming 75% of needs every day); or 3) control (consuming 100% of needs every day) for 24 wk. RESULTS: The VAT:SAT ratio did not change in any group. The FFM:total mass ratio increased in both ADF (0.03 ± 0.00) and CR (0.03 ± 0.01) compared to the control group (P < 0.01), with no differences between the intervention groups. Circulating leptin decreased in both the ADF group (−18 ± 6%) and CR group (−31 ± 10%) relative to the control group (P < 0.05), with no differences between the intervention groups. Circulating levels of adiponectin, resistin, IL-6, and TNF-α did not change in either intervention group relative to the control group. CONCLUSION: ADF and CR similarly improve the FFM:total mass ratio and reduce leptin after a 24-wk intervention.

The physiological and metabolic effects of experimental overfeeding have been extensively studied, yet only few studies have assessed overfeeding effects on eating behaviors and psychological constructs. We analyzed two 8-week overfeeding studies, the PROOF Study (N = 25; 16 males; 16 African American; 24.1 years; 25.1 kg/m2, inpatient) and the EAT Study (N = 35; 29 males; 20 White; 26.7 years; 25.5 kg/m2, free-living). In both studies, participants were overfed 40% above baseline (daily) energy requirements for eight weeks, consuming all meals under direct supervision. We assessed eating attitudes and behaviors, eating disorder symptoms, and body image via validated questionnaires and visual analog scales at baseline, week (W) 4, and W8, and at two (PROOF: W16-Post, W24-Post) and three (EAT: W12-Post, W20-Post, W32-Post) follow-up visits, respectively. Hunger, desire to eat, and food cravings (carbohydrates, total cravings) decreased during overfeeding in both studies (all Cohen's d effect sizes ≥0.3, all p ≤ .048). Depressive symptoms and fear of fatness increased in both studies (all Cohen's d ≥ 0.4, p ≤ .020), though they were still within normal limits (t-scores ~43–49). Body dissatisfaction increased in both studies during overfeeding (all Cohen's d ≥ 0.4, all p ≤ .044) and remained increased during follow-up (PROOF: W16-Post, Cohen's d = 0.9, p = .004; EAT: W12-Post and W20-Post, all Cohen's d ≥ 0.4, all p ≤ .037). Overfeeding was associated with some deleterious effects, though most returned to baseline during follow-up. However, increases in body dissatisfaction remained up to three months post-overfeeding, highlighting the need to address body image disturbance among people who experience weight gain, even if much of the gained weight is subsequently lost. Trial registration The PROOF Study ( ClinicalTrials.gov Identifier NCT00565149 ); the EAT Study ( ClinicalTrials.gov Identifier NCT01672632 ).

Introduction: Caloric restriction (CR) improves cardiometabolic risk, even among individuals without obesity. However, it is unclear whether these aging-related benefits are mediated by weight loss. Mediation analyses inform mechanisms underlying relationships between an exposure and outcome. Using mediation analyses, our aim was to test if 2-year weight loss mediates the beneficial effects of CR on cardiometabolic risk markers in individuals without obesity. Methods: Participants without obesity were randomized 2:1 to CR or ad libitum (AL) as part of the 2-year trial, Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE). The CR group aimed to enact 25% CR for 2 years, while AL maintained habitual energy intake. Baseline and year 2 assessments included weight and cardiometabolic risk markers. Using the approaches of Valeri and VanderWeele, mediation was quantified as the natural indirect effect (NIE), defined as the impact of an exposure on an outcome through a mediator. Here, the NIE was the effect of CR (exposure) on cardiometabolic risk markers (outcome) that was accounted for by weight change (mediator). Results: In total, 117 and 71 participants in the CR and AL groups, respectively, completed the trial. The CR group achieved 11.9 (± 0.7)% CR and 7.6 (± 0.3) kg of weight loss ( P < 0.01 versus AL). Weight loss significantly mediated the CR-induced improvements in total cholesterol (NIE = -10.4 ± 3.5 mg/dL), low-density lipoprotein cholesterol (NIE = -8.5 ± 2.8 mg/dL), high-density lipoprotein cholesterol (NIE = 2.9 ± 1.3 mg/dL), triglycerides (NIE = -0.20 ± 0.05 log mg/dL), the homeostatic model assessment of insulin resistance (NIE = -0.22 ± 0.06), and C-reactive protein (NIE = -0.39 ± 0.15 log ug/mL) ( P ≤ 0.02). Weight loss did not mediate CR-induced reductions in systolic (NIE = -0.9 ± 1.4 mmHg) and diastolic (NIE = -1.0 ± 1.1 mmHg) blood pressure ( P ≥ 0.37). Conclusion: In individuals without obesity, CR-induced improvements in multiple cardiometabolic risk markers are driven by weight loss after 2 years. These findings emphasize that, even in individuals without obesity, weight loss after prolonged CR plays a role in improving cardiometabolic disease risk; however, some CR benefits still occur independent of weight loss.

Dynamic phosphorus MRS ((31)P-MRS) is a method used for in vivo studies of skeletal muscle energetics including measurements of phosphocreatine (PCr) resynthesis rate during recovery of submaximal exercise. However, the molecular events associated with the PCr resynthesis rate are still under debate. We assessed vastus lateralis PCr resynthesis rate from (31)P-MRS spectra collected from healthy adults as part of the CALERIE II study (caloric restriction) and assessed associations between PCr resynthesis and muscle mitochondrial signature transcripts and proteins (NAMPT, NQO1, PGC-1α, and SIRT1). Regression analysis indicated that higher concentration of nicotinamide phosphoribosyltransferase (NAMPT) protein, a mitochondrial capacity marker, was associated with faster PCr resynthesis. However, PCr resynthesis was not associated with greater physical fitness (VO(2) peak) or messenger ribonucleic acid levels of mitochondrial function markers such as NQO1, PGC-1α, and SIRT1, suggesting that the impact of these molecular signatures on PCr resynthesis may be minimal in the context of an acute exercise bout. Together, these findings suggest that (31)P-MRS based PCr resynthesis may represent a valid non-invasive surrogate marker of mitochondrial NAMPT in human skeletal muscle.

International audience; This review details the proceedings of a Pennington Biomedical scientific symposium titled, "What Should I Eat and Why? The Environmental, Genetic, and Behavioral Determinants of Food Choice." The symposium was designed to review the literature about energy homeostasis, particularly related to food choice and feeding behaviors, from psychology to physiology. This review discusses the intrinsic determinants of food choice, including biological mechanisms (genetics), peripheral and central signals, brain correlates, and the potential role of the microbiome. This review also address the extrinsic determinants (environment) of food choice within our physical and social environments. Finally, this review reports the current treatment practices for the clinical management of eating-induced overweight and obesity. An improved understanding of these determinants will inform best practices for the clinical treatment and prevention of obesity. Strategies paired with systemic shifts in our public health policies and changes in our "obesogenic" environment will be most effective at attenuating the obesity epidemic.

In vitro and rodent studies suggest that pioglitazone, a thiazolidinedione, can promote adipogenesis in adipose tissue (AT); however, there is a lack of in vivo studies in humans to support these findings. The objectives of this randomised, placebo-controlled, parallel-arm trial were to test if pioglitazone stimulates in vivo adipogenesis in the subcutaneous adipose tissue depots and if these measures were related to metabolic health outcomes in women with obesity. Forty-one healthy women with obesity (20 black; 21 white; 29 ± 6 years; BMI 32.0 ± 1.7 kg/m2; 44.0 ± 3.6% body fat) were randomised to consume 30 mg/day of pioglitazone (n = 21) or placebo (n = 20) for 16 weeks. SAS v9.4 was used to generate the block randomisation code sequence (stored in password-protected files) with a 1:1 allocation ratio. The participants and study staff involved in assessing and analysing data outcomes were blinded to the group assignments. The trial was conducted at Pennington Biomedical Research Center and ended in 2016. At baseline and post-intervention, subcutaneous abdominal (scABD) and femoral (scFEM) AT biopsies were collected, and in vivo cellular kinetics (primary endpoint of the trial) were assessed by an 8 week labelling protocol of deuterium (2H) into the DNA of adipose cells. Body composition was measured by dual-energy x-ray absorptiometry (DXA), scABD and visceral AT (VAT) by MRI, ectopic fat by 1H-MRS, and insulin sensitivity by an OGTT. After the 16 week intervention, there was a significant decrease in visceral fat (VAT:total abdominal AT [as a %]; p = 0.002) and an increase in the Matsuda index (i.e. improved insulin sensitivity; p = 0.04) in the pioglitazone group relative to the placebo group. A significant increase in the formation of new adipocytes was observed in the scFEM (Δ = 3.3 ± 1.6%; p = 0.04) but not the scABD depot (Δ = 2.0 ± 2.1%; p = 0.32) in the pioglitazone group relative to the placebo group. No serious adverse events were reported. Pioglitazone may elicit distinct differences in in vivo adipogenesis in subcutaneous adipose depots in women with obesity, with increased rates in the protective scFEM. Trial registration ClinicalTrials.gov NCT01748994 Funding This study was funded by R01DK090607, P30DK072476, and R03DK112006 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health. The Robert C. and Veronica Atkins Foundation.

Whole-room indirect calorimeters have been used to study human metabolism for more than a century. These studies have contributed substantial knowledge to the assessment of nutritional needs and the regulation of energy expenditure and substrate oxidation in humans. However, comparing results from studies conducted at different sites is challenging because of a lack of consistency in reporting technical performance, study design, and results. In May 2019, an expert panel was convened to consider minimal requirements for conducting and reporting the results of human whole-room indirect calorimeter studies. We propose Room Indirect Calorimetry Operating and Reporting Standards, version 1.0 (RICORS 1.0) to provide guidance to ensure consistency and facilitate meaningful comparisons of human energy metabolism studies across publications, laboratories, and clinical sites.

OBJECTIVE This study aimed to investigate a novel approach for determining the effects of energy-standardized dinner meals (high-fat and low-fat) on respiratory exchange ratio (RER) dynamics and metabolic flexibility. METHODS Using a randomized crossover study design, energy expenditure, RER, and macronutrient oxidation rates were assessed in response to a single dinner meal during an overnight stay in a whole-body room calorimeter. Eight healthy adults completed two overnight chamber stays while fed either a high-fat (60% fat, 20% carbohydrate [CHO], 20% protein; food quotient [FQ] = 0.784) or low-fat (20% fat, 60% CHO, 20% protein; FQ = 0.899) dinner containing 40% of daily energy requirements. RESULTS Following the low-fat meal, CHO oxidation first increased before decreasing, resulting in a 12-hour RER:FQ ratio close to 1.0 (0.986 ± 0.019, P = 0.06) and therefore resulting in a 12-hour equilibrated fat balance (29 ± 76 kcal/12 hours). Following the high-fat meal, participants had a RER:FQ ratio above 1.0 (1.061 ± 0.017, P

Over the past 10 to 15 years, intermittent fasting has emerged as an unconventional approach to reduce body weight and improve metabolic health beyond simple calorie restriction. In this review, we summarize findings related to Ramadan and Sunnah fasting. We then discuss the role of caloric restriction not only as an intervention for weight control, but importantly, as a strategy for healthy aging and longevity. Finally, we review the four most common intermittent fasting (IF) strategies used to date for weight management and to improve cardiometabolic health. Weight loss is common after IF, but does not appear to be different than daily caloric restriction when compared directly. IF may also provide additional cardiometabolic benefit, such as insulin sensitization, that is independent from weight loss. While no specific fasting regimen stands out as superior at this time, there is indeed heterogeneity in responses to these different IF diets. This suggests that one dietary regimen may not be ideally suited for every individual. Future studies should consider strategies for tailoring dietary prescriptions, including IF, based on advanced phenotyping and genotyping prior to diet initiation.

CONTEXT: Eating habits and food craving are strongly correlated with weight status. It is currently not well understood how psychological and behavioral factors influence both weight loss and weight regain. OBJECTIVE: To examine the associations between psychological and behavioral predictors with weight changes and energy intake in a randomized controlled trial on weight loss. DESIGN AND SETTING: The Prevention of Obesity Using Novel Dietary Strategies is a dietary intervention trial that examined the efficacy of 4 diets on weight loss over 2 years. Participants were 811 overweight (body mass index, 25-40.9 kg/m(2); age, 30-70 years) otherwise healthy adults. RESULTS: Every 1-point increase in craving score for high-fat foods at baseline was associated with greater weight loss (-1.62 kg, P = .0004) and a decrease in energy intake (r = -0.10, P = .01) and fat intake (r = -0.16, P

Objective This study aimed to describe the energy expenditure (EE) and macronutrient oxidation response to an individualized nonshivering cold exposure in young healthy adults. Methods Two different groups of 44 (study 1: 22.1 [SD 2.1] years old, 25.6 [SD 5.2] kg/m(2), 34% men) and 13 young healthy adults (study 2: 25.6 [SD 3.0] years old, 23.6 [SD 2.4] kg/m(2), 54% men) participated in this study. Resting metabolic rate (RMR) and macronutrient oxidation rates were measured by indirect calorimetry under fasting conditions in a warm environment (for 30 minutes) and in mild cold conditions (for 65 minutes, with the individual wearing a water-perfused cooling vest set at an individualized temperature adjusted to the individual's shivering threshold). Results In study 1, EE increased in the initial stage of cold exposure and remained stable for the whole cold exposure (P < 0.001). Mean cold-induced thermogenesis (9.56 +/- 7.9 kcal/h) was 13.9% +/- 11.6% of the RMR (range: -14.8% to 39.9% of the RMR). Carbohydrate oxidation decreased during the first 30 minutes of the cold exposure and later recovered up to the baseline values (P < 0.01) in parallel to opposite changes in fat oxidation (P < 0.01). Results were replicated in study 2. Conclusions A 1-hour mild cold exposure individually adjusted to elicit maximum nonshivering thermogenesis induces a very modest increase in EE and a shift of macronutrient oxidation that may underlie a shift in thermogenic tissue activity. This study was supported by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393 and PTA 12264-I); the Retos de la Sociedad (DEP2016-79512-R) and European Regional Development Funds (ERDF); the Spanish Ministry of Education (FPU13/04365, FPU14/04172, and FPU15/04059); the Fundacion Iberoamericana de Nutricion; the Redes Tematicas de Investigacion Cooperativa (RETIC, red de Salud Materno Infantil y del Desarrollo 16/0022); the AstraZeneca HealthCare Foundation; the University of Granada Plan Propio de Investigación 2016 excellence actions (Unit of Excellence on Exercise and Health and Plan Propio de Investigacion 2018: Programa Contratos-Puente and Programa Perfeccionamiento de Doctores); the Junta de Andalucía, Consejeria de Conocimiento, Investigación y Universidades (ERDF; SOMM17/6107/UGR); and the Fundación Alfonso Maríin Escudero.

Metabolic flexibility to lipid (MetFlex-lip) is the capacity to adapt lipid oxidation to lipid availability. Hypothetically, impaired MetFlex-lip in skeletal muscle induces accumulation of lipid metabolites that interfere with insulin signaling. Our aim was to compare MetFlex-lip during exercise in subjects with low (Low_IS) vs. high (High_IS) insulin sensitivity. Twenty healthy men were designated as Low_IS or High_IS on the basis of the median of the homeostatic model assessment of insulin resistance index. Groups had similar age, body mass index, and maximum oxygen uptake (V̇o2max). Subjects cycled at 50% V̇o2max until expending 650 kcal. Adaptation in lipid oxidation was calculated as the drop in respiratory quotient (RQ) at the end of exercise vs. the maximum RQ (ΔRQ). Lipid availability was calculated as the increase in circulating nonesterified fatty acids (NEFA) at the end of exercise vs. the minimum NEFA (ΔNEFA). ΔRQ as a function of ΔNEFA was used to determine MetFlex-lip. On average, RQ and circulating NEFA changed similarly in both groups. However, ΔRQ correlated with ΔNEFA in High_IS ( r = −0.83, P < 0.01) but not in Low_IS ( r = −0.25, P = 0.48) subjects. Thus the slope of the ΔRQ vs. ΔNEFA relationship was steeper in High_IS vs. Low_IS subjects (−0.139 ± 0.03 vs. −0.025 ± 0.03 RQ·mmol−1·l−1, respectively; P < 0.05), with similar intercepts. We conclude that in subjects with High_IS lipid-to-carbohydrate oxidation ratio adapts to the increased circulating NEFA availability during exercise. Such MetFlex-lip appears impaired in subjects with Low_IS. Whether a cause-effect relationship exists between impaired MetFlex-lip and low insulin sensitivity remains to be determined.

The storage of lipids in the form of triglycerides (TGs) and the de novo synthesis (lipogenesis) of fatty acids from nonlipid precursors [de novo lipogenesis (DNL)] are important functions of adipose tissue (AT) that influence whole-body metabolism. Yet, few studies have reported in vivo estimates of adipose lipid kinetics in humans. Fifty-two women with obesity (27 African-American and 25 Caucasian; 29.7 ± 5.5 years; BMI 32.2 ± 2.8 kg/m(2); 44.3 ± 4.0% body fat) were enrolled in the study. In vivo synthesis (or replacement) of TGs (f(TG)) as well as the synthesis of the fatty acid, palmitate [a measure of adipose DNL (f(DNL))], were assessed using an 8 week incorporation of deuterium into lipids (glycerol and palmitate moieties of TGs) in subcutaneous abdominal (scABD) and subcutaneous femoral (scFEM) AT. We report, for the first time, significant race differences in both TG synthesis and absolute DNL, with Caucasians having higher f(TG) and f(DNL) as compared with African-Americans. The DNL contribution to newly synthesized TG (corrected f(DNL)) was not different between races. Interestingly, our findings also show that the scFEM adipose depot had higher TG replacement rates relative to the scABD. Finally, the replacement rate of TG (f(TG)) was negatively correlated with changes in body weight over the 8 week labeling period. Our results provide the first evidence that in vivo TG replacement (synthesis and breakdown) rates differ by ethnicity. In addition, TG turnover varies by depot location in humans, implying an increased capacity for TG storage and higher lipolytic activity in the scFEM AT.

To date, human studies show that brown adipose tissue (BAT) contributes a small yet highly variable amount to overall energy expenditure. No studies have shown a decrease in body weight with cold-induced BAT activation, and existing pharmacological studies suggest that BAT activation via the sympathetic nervous system may result in increased heart rate and systolic blood pressure. Furthermore, even though the amount and/or activity of BAT have been shown to vary with seasons, such variation does not seem to be translated into weight changes. Collectively, these findings do not support the use of BAT activation for weight loss in humans; however, the potential role of BAT in counteracting the metabolic adaptation observed with weight loss is suggested. Although the role of BAT in weight control is currently unsubstantiated, BAT may play a role in improving insulin sensitivity in humans.

OBJECTIVE This study aimed to identify factors that may predispose women to excess gestational weight gain (GWG). METHODS Seventy-two healthy women with obesity (30 class I, 24 class II, 18 class III) expecting a singleton pregnancy were studied at 13 to 16 weeks gestation. Energy expenditure (EE) was measured during sleep (SleepEE, average EE from 0200-0500 hours) in a whole-room calorimeter, and total daily EE (TDEE) over 7 days using doubly labeled water. Glucose, insulin, thyroid hormones, and catecholamines were measured. RESULTS Body composition explained 70% variability in SleepEE, and SleepEE accounted for 67% to 73% of TDEE. Though there was no evidence of consistent low metabolism, there was considerable variability. Low SleepEE was associated with insulin resistance and low triiodothyronine concentrations (both P = 0.01). Physical activity level was 1.47 ± 0.02. For women with SleepEE within 100 kcal/d of their predicted EE, TDEE was significantly less than the estimate (2,530 ± 91 vs. 2,939 kcal/d; P

Prevalence of diabetes and obesity in Mexican Pima Indians is low, while prevalence is high in Pima Indians in the United States (US); although lifestyle likely accounts for much of the difference, the role of genetic factors is not well-explored. To examine this, we genotyped 359 single nucleotide polymorphisms, including established type 2 diabetes and obesity variants from genome-wide association studies (GWAS) and 96 random markers, in 342 Mexican Pimas. A multimarker risk score of obesity variants was associated with body mass index (BMI; β = 0.81 kg/m(2) per SD, P = 0.0066). The mean value of the score was lower in Mexican Pimas than in US Pimas (P = 4.3×10(−11)), and differences in allele frequencies at established loci could account for ~7% of the population difference in BMI; however, the difference in risk scores was consistent with evolutionary neutrality given genetic distance. To identify loci potentially under recent natural selection, allele frequencies at 283 variants were compared between US and Mexican Pimas, accounting for genetic distance. The largest differences were seen at HLA markers (e.g., rs9271720, difference = 0.75, P = 8.7×10(−9)); genetic distances at HLA were greater than at random markers (P = 1.6×10(−46)). Analyses of GWAS data in 937 US Pimas also showed sharing of alleles identical by descent at HLA that exceeds its genomic expectation (P = 7.0×10(−10)). These results suggest that, in addition to the widely-recognized balancing selection at HLA, recent directional selection may also occur, resulting in marked allelic differentiation between closely related populations.

Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference 'Diet and Cardiometabolic Health - Beyond Calories', and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential 'beyond calories' mechanisms may lead to new strategies for attenuating the obesity crisis.

INTRODUCTION: The ability to maintain functional independence in a rapidly aging population results in an increased life expectancy without corresponding increases in health care costs. The accelerated decline in VO(2peak) after the age of 65 is primarily due to peripheral tissue changes rather than centrally mediated factors. The purpose of this study was to determine if the PRIME (Peripheral Remodeling through Intermittent Muscular Exercise) approach, consisting of a low mass, high repetition/duration skeletal muscle focused training regimen would provide superior functional benefits in participants above 70 years old and at risk for losing functional independence. METHODS: In this clinical trial, 107 participants were randomized to four weeks of either standard aerobic exercise training (AT) or PRIME [Phase 1]. This was followed by eight weeks of a progressive whole-body aerobic and resistance training (AT+RT) for all participants [Phase 2]. The major outcome measures were cardiorespiratory fitness (peak oxygen consumption-VO(2peak)), muscular fitness (1 repetition maximal strength -1RM) and physical function (Senior Fitness Test scores-SFT). Results were analyzed under a pro-protocol criterion. RESULTS: Thirty-eight PRIME and 38 AT participants completed the 3-month protocols. VO(2peak), 1RM, and SFT scores all increased significantly after 12 weeks for both treatment groups (p

BackgroundSeveral indirect calorimetry (IC) instruments are commercially available, but comparative validity and reliability data are lacking. Existing data are limited by inconsistencies in protocols, subject characteristics, or single-instrument validation comparisons. The aim of this study was to compare accuracy and reliability of metabolic carts using methanol combustion as the cross-laboratory criterion.MethodsEight 20-minute methanol burn trials were completed on 12 metabolic carts. Respiratory exchange ratio (RER) and percent O-2 and CO2 recovery were calculated.ResultsFor accuracy, 1 Omnical, Cosmed Quark CPET (Cosmed), and both Parvos (Parvo Medics trueOne 2400) measured all 3 variables within 2% of the true value; both DeltaTracs and the Vmax Encore System (Vmax) showed similar accuracy in measuring 1 or 2, but not all, variables. For reliability, 8 instruments were shown to be reliable, with the 2 Omnicals ranking best (coefficient of variation [CV] ConclusionsOmnical, Parvo, Cosmed, and DeltaTrac had greater accuracy and reliability. The small number of instruments tested and expected differences in gas calibration variability limits the generalizability of conclusions. Finally, humidity and temperature could be modified in the laboratory to optimize IC conditions.

We previously showed that fetal exposure to maternal type 1 diabetes (T1D) is associated with altered glucose-stimulated insulin secretion in adult offspring. Here, we investigated whether this β-cell defect displays a sex dimorphism. Twenty-nine adult nondiabetic offspring of T1D mothers (ODMs) were compared with 29 nondiabetic offspring of T1D fathers. We measured early insulin secretion in response to oral glucose and insulin secretion rate in response to intravenous glucose ramping. Insulin sensitivity and body composition were assessed by a euglycemic, hyperinsulinemic clamp and dual-energy X-ray absorptiometry, respectively. In response to oral glucose, male and female ODMs displayed a reduced insulin secretion. In contrast, in response to graded intravenous glucose infusion, only female ODMs (not males) exhibited decreased insulin secretion. There was no defect in response to combined intravenous arginine and glucose, suggesting that male and female ODMs exhibit a functional β-cell defect rather than a reduced β-cell mass. In conclusion, fetal exposure to maternal diabetes predisposes to β-cell dysfunction in adult male and female offspring. This β-cell defect is characterized by a sexual dimorphism following intravenous glucose stimulation., Insulin secretion was evaluated in adults who have been exposed in utero to maternal T1D. Only women (not men) exhibited decreased insulin secretion in response to intravenous glucose.

A noninvasive method to estimate muscle mass based on creatine ( methyl-d3) (D3-creatine) dilution using fasting morning urine was evaluated for accuracy and variability over a 3- to 4-mo period. Healthy older (67- to 80-yr-old) subjects ( n = 14) with muscle wasting secondary to aging and four patients with chronic disease (58–76 yr old) fasted overnight and then received an oral 30-mg dose of D3-creatine at 8 AM ( day 1). Urine was collected during 4 h of continued fasting and then at consecutive 4- to 8-h intervals through day 5. Assessment was repeated 3–4 mo later in 13 healthy subjects and 1 patient with congestive heart failure. Deuterated and unlabeled creatine and creatinine were measured using liquid chromatography–tandem mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by whole body MRI and 24-h urine creatinine, and lean body mass (LBM) was measured by dual-energy X-ray absorptiometry (DXA). D3-creatinine urinary enrichment from day 5 provided muscle mass estimates that correlated with MRI for all subjects ( r = 0.88, P < 0.0001), with less bias [difference from MRI = −3.00 ± 2.75 (SD) kg] than total LBM assessment by DXA, which overestimated muscle mass vs. MRI (+22.5 ± 3.7 kg). However, intraindividual variability was high with the D3-creatine dilution method, with intrasubject SD for estimated muscle mass of 2.5 kg vs. MRI (0.5 kg) and DXA (0.8 kg). This study supports further clinical validation of the D3-creatine method for estimating muscle mass. NEW & NOTEWORTHY Measurement of creatine ( methyl-d3) (D3-creatine) and D3-creatinine excretion in fasted morning urine samples may be a simple, less costly alternative to MRI or dual-energy X-ray absorptiometry (DXA) to calculate total body muscle mass. The D3-creatine enrichment method provides estimates of muscle mass that correlate well with MRI, and with less bias than DXA. However, intraindividual variability is high with the D3-creatine method. Studies to refine the spot urine sample method for estimation of muscle mass may be warranted.

While the first reported case of SARS-CoV-2 occurred in Wuhan, China, in December 2019, giving the name to the disease COVID-19, the World Health Organization declared this a Public Health Emergency of International Concern on January 30, 2020, and a pandemic on March 11, 2020 Persons with obesity indeed have increased rates of comorbid conditions, often have impaired immune responses to viral threats and abnormal proinflammatory and prothrombotic profiles, and experience stigma in health care settings where they are at a disadvantage because of their size (limited use of diagnostic equipment and therapeutic maneuvers), all factors driving COVID-19 complications and mortality (1) [ ]the annual Obesity Journal Symposium was held virtually at ObesityWeek with an outstanding and diverse group of papers and young scientists presenting their work

Reduced mitochondrial capacity in skeletal muscle has been observed in obesity and type 2 diabetes. In humans, the aetiology of this abnormality is not well understood but the possibility that it is secondary to the stress of nutrient overload has been suggested. To test this hypothesis, we examined whether sustained overfeeding decreases skeletal muscle mitochondrial content or impairs function. Twenty-six healthy volunteers (21 men, 5 women, age 25.3 ± 4.5 years, BMI 25.5 ± 2.4 kg/m2) underwent a supervised protocol consisting of 8 weeks of high-fat overfeeding (40% over baseline energy requirements). Before and after overfeeding, we measured systemic fuel oxidation by indirect calorimetry and performed skeletal muscle biopsies to measure mitochondrial gene expression, content and function in vitro. Mitochondrial function in vivo was measured by 31P NMR spectroscopy. With overfeeding, volunteers gained 7.7 ± 1.8 kg (% change 9.8 ± 2.3). Overfeeding increased fasting NEFA, LDL-cholesterol and insulin concentrations. Indirect calorimetry showed a shift towards greater reliance on lipid oxidation. In skeletal muscle tissue, overfeeding increased ceramide content, lipid droplet content and perilipin-2 mRNA expression. Phosphorylation of AMP-activated protein kinase was decreased. Overfeeding increased mRNA expression of certain genes coding for mitochondrial proteins (CS, OGDH, CPT1B, UCP3, ANT1). Despite the stress of nutrient overload, mitochondrial content and mitochondrial respiration in muscle did not change after overfeeding. Similarly, overfeeding had no effect on either the emission of reactive oxygen species or on mitochondrial function in vivo. Skeletal muscle mitochondria are significantly resilient to nutrient overload. The lower skeletal muscle mitochondrial oxidative capacity in human obesity is likely to be caused by reasons other than nutrient overload per se. ClinicalTrials.gov NCT01672632.

New treatment approaches to weight loss and weight loss maintenance in humans are critical. Given its potential role in stimulating energy expenditure, brown adipose tissue (BAT) activation has become a trending topic as an anti-obesity treatment. Most studies on BAT stimulation have been conducted in rodents and used cold stimulation. To date, few human trials exist that tested the effect of cold exposure on BAT. Those studies show that BAT contributes a small amount to overall energy metabolism which is unlikely to cause weight loss. Nonetheless, improvements in glucose metabolism have been demonstrated in humans. While new pharmacological approaches demonstrate some contribution of BAT to overall energy expenditure, the potential cardiovascular risk (increased heart rate and blood pressure to sustain the extra energy expenditure) may preclude their use. There is no convincing evidence yet to indicate that BAT may be a viable pharmaceutical target for body weight loss or even weight loss maintenance. More research is needed to confirm the relevance of BAT and beige tissue to whole-body energy metabolism in humans.