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Study Question: Is resting energy expenditure (REE) altered in women with polycystic ovary syndrome (PCOS)?, Summary Answer: Women with PCOS have a reduction in REE, when corrected for fat-free mass, independent of PCOS clinical phenotypes and BMI categories., What Is Known Already: Obesity is an important issue in women with PCOS, in terms of frequency and pathophysiological implications. It has been hypothesized that obesity may be favoured by alterations in REE, but the studies have been limited and conflicting., Study Design, Size, Duration: This case-control study was a comparison of 266 women with PCOS and 51 healthy controls, recruited in the Verona 3P study from 2010 to 2021., Participants/materials, Setting, Methods: Women with PCOS diagnosed by the Rotterdam criteria, with normal thyroid function and no interfering medications, were referred to the outpatient clinic of a tertiary care centre of endocrinology and metabolism for a measurement of REE. Healthy controls were recruited in the same period and submitted to the same procedure. In all subjects, REE was measured by indirect calorimetry and serum androgens were measured by LC-MS/MS. In women with PCOS, insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp., Main Results and the Role of Chance: REE was similar in women with PCOS and controls. However, REE corrected for fat-free mass (REE/FFM) was significantly lower in women with PCOS than in controls (31.8 ± 4.0 vs 35.4 ± 3.9 kcal/kgFFM·day, P < 0.001). REE/FFM did not differ between normal-weight, overweight, or obese women with PCOS, and each of these subgroups showed lower REE/FFM values than controls. Reduced REE/FFM values were found in each phenotype of the syndrome. In multiple regression analysis, REE/FFM was independently associated with age and PCOS status, but not with fat mass. In PCOS women, REE/FFM was independently and directly associated with ovarian follicle number., Limitations, Reasons for Caution: Limitations of the study are the cross-sectional design, which limits the causal inference of the results, and the unavailability of precise information about lifestyle factors, which may be potential confounders. Further prospective studies are needed to establish the importance of this phenomenon in contributing to the weight excess of PCOS., Wider Implications of the Findings: A reduction of REE could potentially favour weight gain in women with PCOS and possibly contribute to the altered metabolic profile typical of this condition, even counteracting the therapeutic strategies aimed to reduce excess body fat in these women. Nevertheless, the presence of this abnormality in both obese/overweight and normal-weight patients suggests that other factors must play a role in this phenomenon., Study Funding/competing Interest(s): This work was supported by academic grants to PM from the University of Verona (FUR 2010-2022). All authors declare no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Context: It remains uncertain whether aging before late adulthood and menopause are associated with fat-free mass and fat mass-adjusted resting energy expenditure (REEadj)., Objectives: We investigated whether REEadj differs between middle-aged and younger women and between middle-aged women with different menopausal statuses. We repeated the age group comparison between middle-aged mothers and their daughters to partially control for genotype. We also explored whether serum estradiol and FSH concentrations explain REEadj in midlife., Methods: We divided 120 women, including 16 mother-daughter pairs, into age groups; group I (n = 26) consisted of participants aged 17 to 21, group II (n = 35) of those aged 22 to 38, and group III (n = 59) of those aged 41 to 58 years. The women in group III were further categorized as pre- or perimenopausal (n = 19), postmenopausal (n = 30), or postmenopausal hormone therapy users (n = 10). REE was assessed using indirect calorimetry, body composition using dual-energy X-ray absorptiometry, and hormones using immunoassays., Results: The REEadj of group I was 126 kcal/day [95% confidence interval (CI): 93-160] higher than that of group III, and the REEadj of group II was 88 kcal/day (95% CI: 49-127) higher. Furthermore, daughters had a 100 kcal/day (95% CI: 63-138 kcal/day) higher REEadj than their middle-aged mothers (all P < .001). In group III, REEadj was not lower in postmenopausal women and did not vary by sex hormone concentrations., Conclusions: We demonstrated that REEadj declines with age in women before late adulthood, also when controlling partially for genetic background, and that menopause may not contribute to this decline., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: We have recently shown that the secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is upregulated in human obesity and that overexpression of scEMC10 promotes, whereas antibody neutralization of circulating scEMC10 prevents diet-induced obesity in mice., Objective: To explore associations of serum scEMC10 with body mass index (BMI), resting metabolism rate (RMR), and age in humans., Design: A cross-sectional study., Setting and Patients: A total of 833 participants from a Chinese physical examination cohort and 191 participants from the Leipzig Obesity Biobank cohort., Main Outcome Measures: Serum scEMC10 concentrations are measured using chemiluminescent immunoassay. RMR is calculated based on measurements from indirect calorimetry with an open-circuit ventilated-hood system., Results: In the Chinese physical examination cohort, a J-shaped nonlinear correlation between BMI and serum scEMC10 was identified in participants where underweight, overweight, and obese people all presented higher serum scEMC10 levels than normal weight people. Participants younger than age 30 years old exhibited significantly higher serum scEMC10 levels than those older than 50 years of age. In addition, participants aged 30 to 40 years also had significantly higher serum scEMC10 levels than those aged 50 to 60 years. In the Leipzig Obesity Biobank cohort, we observed a significantly negative correlation between serum scEMC10 and resting energy expenditure after adjusting for BMI. Participants in the highest quartile of serum scEMC10 levels had significantly lower RMR than those in the first quartile. RMR had an independently inverse association with serum scEMC10., Conclusions: Serum scEMC10 levels are negatively associated with age and RMR in humans., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Energy expenditure predictive equations can generate inaccurate estimates for overweight or obese individuals., Objective: The objective of this review was to determine which predictive equations for resting energy expenditure (REE) and total energy expenditure (TEE) have the lowest bias and the highest precision in adults with overweight and obesity., Data Sources: Searches were performed in January 2022 in MEDLINE, Web of Science, Scopus, CENTRAL, and the gray literature databases., Data Extraction: Meta-analyses were performed with equations included in more than 1 study. The DerSimonian and Laird random-effects model and the I2 statistic were used to quantify heterogeneity in the quantitative analyses. The Egger test was performed to assess potential publication biases, and metaregressions were conducted to explore the heterogeneity. Findings were presented separated by participants' body mass index classification (overweight and obesity)., Data Analysis: Sixty-one studies were included. The FAO/WHO/UNU (1985) equation, which uses only body weight in its formula, showed the lowest bias in estimating REE (mean difference [MD] = 8.97 kcal; 95% CI = -26.99; 44.94). In the subgroup analysis for individuals with obesity, the Lazzer (2007) equation showed the lowest bias (MD = 4.70 kcal; 95% CI = -95.45; 104.86). The Harris-Benedict equation (1919) showed the highest precision values for individuals with overweight (60.65%) and for individuals with obesity (62.54%). Equations with body composition data showed the highest biases. The equation proposed by the Institute of Medicine (2005) showed the lowest bias (MD = -2.52 kcal; 95% CI = -125.94; 120.90) in estimating the TEE. Most analyses showed high heterogeneity (I2 > 90%). There was no evidence of publication bias., Conclusion: For individuals with overweight, the FAO/WHO/UNU (1985) and the Harris-Benedict equations (1919) showed the lowest bias and the highest precision in predicting the REE, respectively. For individuals with obesity, the Harris-Benedict equation (1919) showed the highest precision and the Lazzer equation (2007) showed the lowest bias. More studies are needed on predictive equations to estimate the TEE., Systematic Review Registration: PROSPERO registration no. CRD42021262969., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Body fat gain associated with menopause has been attributed to estradiol (E2) withdrawal. Hypoestrogenism is unlikely to be the only contributing factor, however., Objective: Given the links between sleep and metabolic health, we examined the effects of an experimental menopausal model of sleep fragmentation on energy metabolism., Methods: Twenty premenopausal women (age 21-45 years) underwent a 5-night inpatient study during the mid-to-late follicular phase (estrogenized; n = 20) and the same protocol was repeated in a subset of the participants (n = 9) following leuprolide-induced E2 suppression (hypo-estrogenized). During each 5-night study, there were 2 nights of unfragmented sleep followed by 3 nights of fragmented sleep. Indirect calorimetry was used to assess fasted resting energy expenditure (REE) and substrate oxidation., Results: Sleep fragmentation in the estrogenized state increased the respiratory exchange ratio (RER) and carbohydrate oxidation while decreasing fat oxidation (all P < 0.01). Similarly, in the hypo-estrogenized state without sleep fragmentation, RER and carbohydrate oxidation increased and fat oxidation decreased (all P < 0.01); addition of sleep fragmentation to the hypo-estrogenized state did not produce further effects beyond that observed for either intervention alone (P < 0.05). There were no effects of either sleep fragmentation or E2 state on REE., Conclusion: Sleep fragmentation and hypoestrogenism each independently alter fasting substrate oxidation in a manner that may contribute to body fat gain. These findings are important for understanding mechanisms underlying propensity to body fat gain in women across the menopause transition., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Daily variation in the thermic effect of food (TEF) is commonly reported and proposed as a contributing factor to weight gain with late eating. However, underlying circadian variability in resting metabolic rate (RMR) is an overlooked factor when calculating TEF associated with eating at different times of the day., Objective: This work aimed to determine whether methodological approaches to calculating TEF contribute to the reported phenomena of daily variation in TEF., Methods: Fourteen overweight to obese but otherwise healthy individuals had their resting and postprandial energy expenditure (EE) measured over 15.5 hours at a clinical research unit. TEF was calculated for breakfast, lunch, and dinner using standard methods (above a baseline and premeal RMR measure) and compared to a method incorporating a circadian RMR by which RMR was derived from a sinusoid curve model and TEF was calculated over and above the continuously changing RMR. Main outcome measures were TEF at breakfast, lunch, and dinner calculated by different methods., Results: Standard methods of calculating TEF above a premeal measured RMR showed that morning TEF (60.8 kcal ± 5.6) (mean ± SEM) was 1.6 times greater than TEF at lunch (36.3 kcal ± 8.4) and 2.4 times greater than dinner TEF (25.2 kcal ± 9.6) (P = .022). However, adjusting for modeled circadian RMR nullified any differences between breakfast (54.1 kcal ± 30.8), lunch (49.5 kcal ± 29.4), and dinner (49.1 kcal ± 25.7) (P = .680)., Conclusion: Differences in TEF between morning and evening can be explained by the underlying circadian resting EE, which is independent of an acute effect of eating., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: The maximal fat oxidation rate (MFO) is higher in aerobically fit vs unfit young men, but this training-related increase in MFO is attenuated in middle-aged men. Further, it has also been found that unfit men with obesity may have an elevated MFO compared to unfit normal-weight men., Objective: Based hereupon, we aimed to investigate whether a fitness-related higher MFO were attenuated in middle-aged women compared to young women. Also, we aimed to investigate if unfit women with obesity have a higher MFO compared to unfit normal-weight women. We hypothesized that the training-related elevated MFO was attenuated in middle-aged women, but that unfit women with obesity would have an elevated MFO compared to unfit normal-weight women., Methods: We recruited 70 women stratified into 6 groups: young fit (n = 12), young unfit (n = 12) middle-aged fit (n = 12), middle-aged unfit (n = 12), unfit young women with obesity (n = 12), and unfit middle-aged women with obesity (n = 10). Body composition and resting blood samples were obtained and MFO was measured by a graded exercise test on a cycle ergometer via indirect calorimetry. Subsequently, a maximal exercise test was performed to establish peak oxygen uptake (V̇O2peak)., Results: Young and middle-aged fit women had a higher MFO compared to age-matched unfit women, and young fit women had a higher MFO compared to fit middle-aged women. Unfit women with obesity, independent of age, had a higher MFO compared to their normal-weight and unfit counterparts., Conclusion: The training-related increase in MFO seems maintained in middle-aged women, and we find that unfit women with obesity, independent of age, have a higher MFO compared to unfit normal-weight women., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Few studies have explored in vivo insulin action on substrate use in women with PCOS. In particular, no data are available in women with different PCOS phenotypes., Objective: The aim of the study was to evaluate insulin action on glucose (Gox) and lipid (Lox) oxidation, nonoxidative glucose metabolism (Gnonox), and serum free fatty acids (FFAs) in different PCOS phenotypes., Methods: Participants included 187 nondiabetic women with PCOS diagnosed according to the Rotterdam criteria. Data from a historical sample of 20 healthy women were used as reference values. Whole-body substrate use data were obtained by the hyperinsulinemic euglycemic clamp associated with indirect calorimetry. Serum androgens were assessed by liquid chromatography-mass spectrometry and equilibrium dialysis., Results: During hyperinsulinemia, the increase of Gox (ΔGox), Gnonox, as well as the suppression of Lox (ΔLox) and serum FFA (Δ% FFA) were altered in each PCOS phenotype. Moreover, Gnonox and Δ% FFA were lower in women with the classic phenotype than in those with the ovulatory or the normoandrogenic phenotypes, and ΔGox was lower in women with the classic than in those with the ovulatory phenotype. In multivariable analysis fat mass and free testosterone were independent predictors of ΔGox, Gnonox, and Δ% FFA, whereas only fat mass predicted ΔLox., Conclusion: In women with PCOS, regardless of phenotype, insulin-mediated substrate use is impaired. This phenomenon is greater in individuals with the classic phenotype. Free testosterone plays an independent role in insulin action abnormalities in glucose and lipid metabolism., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Accumulating evidence links brown adipose tissue (BAT) to increased cold-induced energy expenditure (CIEE) and regulation of lipid metabolism in humans. BAT has also been proposed as a novel source for biologically active lipid mediators including polyunsaturated fatty acids (PUFAs) and oxylipins. However, little is known about cold-mediated differences in energy expenditure and various lipid species between individuals with detectable BAT positive (BATpos) and those without BAT negative (BATneg)., Methods: Here we investigated a unique cohort of matched BATpos and BATneg individuals identified by 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography ([18F]-FDG PET/CT). BAT function, CIEE, and circulating oxylipins, were analyzed before and after short-term cold exposure using [18F]-FDG PET/CT, indirect calorimetry, and high-resolution mass spectrometry, respectively., Results: We found that active BAT is the major determinant of CIEE since only BATpos individuals experienced significantly increased energy expenditure in response to cold. A single bout of moderate cold exposure resulted in the dissipation of an additional 20 kcal excess energy in BATpos but not in BATneg individuals. The presence of BAT was associated with a unique systemic PUFA and oxylipin profile characterized by increased levels of anti-inflammatory omega-3 fatty acids as well as cytochrome P450 products but decreased concentrations of some proinflammatory hydroxyeicosatetraenoic acids when compared with BATneg individuals. Notably, cold exposure raised circulating levels of various lipids, including the recently identified BAT-derived circulating factors (BATokines) DiHOME and 12-HEPE, only in BATpos individuals., Conclusions: In summary, our data emphasize that BAT in humans is a major contributor toward cold-mediated energy dissipation and a critical organ in the regulation of the systemic lipid pool., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The human thrifty phenotype hypothesis presupposes that lower 24-hour (24h) energy expenditure (24EE) during famine preserves body mass and promotes survival. The prevailing view defines thrifty individuals as having a lower 24EE during fasting. However, it is also plausible that the greater decline in 24EE during fasting in thrifty individuals is due to higher 24EE during energy balance conditions (ENBAL). Herein, we provide evidence that this is indeed the case., Methods: In 108 healthy subjects, 24EE was measured in a whole-room indirect calorimeter both during ENBAL and 24h fasting conditions. Subjects were categorized as thrifty or spendthrift based on the median value (-162 kcal/day) of the difference in 24EE (adjusted for body composition) between fasting and ENBAL conditions. Concomitant 24h urinary catecholamines were assessed by liquid chromatography-mass spectrometry., Results: Compared to ENBAL, 24EE decreased during 24h fasting by 172 kcal/day (standard deviation = 93; range, -470 to 122). A greater-than-median decrease in 24EE ("thriftier" phenotype) was due to higher 24EE during ENBAL (+124 kcal/day; P < 0.0001) but not to lower 24EE during fasting (P = 0.35). Greater fasting-induced increase in epinephrine was associated with concomitant lower decrease in 24EE (r = 0.27; P = 0.006)., Main Conclusion: The greater decrease in 24EE during acute fasting (which characterizes the thrifty phenotype) is not due to reduced metabolic rate during fasting but to a relatively higher 24EE during feeding conditions, and this decrease in 24EE during fasting is accompanied by a smaller increase in epinephrine. These results recharacterize the prevailing view of the short-term 24EE responses that define the human metabolic phenotypes. Clinical Trials: NCT00523627, NCT00687115, NCT02939404., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Background: The question of whether there is daytime time variation in diet-induced thermogenesis (DIT) has not been clearly answered. Moreover, it is unclear whether a potential diurnal variation in DIT is preserved during hypocaloric nutrition., Objective: We hypothesized that DIT varies depending on the time of day and explored whether this physiological regulation is preserved after low-calorie compared with high-calorie intake., Design: Under blinded conditions, 16 normal-weight men twice underwent a 3-day in-laboratory, randomized, crossover study. Volunteers consumed a predetermined low-calorie breakfast (11% of individual daily kilocalorie requirement) and high-calorie dinner (69%) in one condition and vice versa in the other. DIT was measured by indirect calorimetry, parameters of glucose metabolism were determined, and hunger and appetite for sweets were rated on a scale., Results: Identical calorie consumption led to a 2.5-times higher DIT increase in the morning than in the evening after high-calorie and low-calorie meals (P < .001). The food-induced increase of blood glucose and insulin concentrations was diminished after breakfast compared with dinner (P < .001). Low-calorie breakfast increased feelings of hunger (P < .001), specifically appetite for sweets (P = .007), in the course of the day., Conclusions: DIT is clearly higher in the morning than in the evening, irrespective of the consumed calorie amount; that is, this physiological rhythmicity is preserved during hypocaloric nutrition. Extensive breakfasting should therefore be preferred over large dinner meals to prevent obesity and high blood glucose peaks even under conditions of a hypocaloric diet., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: We examined whether obese individuals have a reduced maximal fat oxidation (MFO) and the intensity that elicit MFO (Fatmax) compared with normal weight and overweight persons, taking into account their level of cardiorespiratory fitness., Methods: The study subjects were 138 sedentary adults (87 women) aged 30.1 ± 13.6 years. Based on their body mass index, subjects were categorized as being of normal weight (n = 66), overweight (n = 48), or obese (n = 24). MFO and Fatmax were determined for all subjects by indirect calorimetry, using a walking graded exercise test. MFO was expressed in absolute terms (g/min) and relative to whole-body lean mass (mg/kgleanmass/min). Cardiorespiratory fitness was assessed via a maximal treadmill test., Results: No differences in absolute MFO and Fatmax values were seen between the obese, normal weight, and overweight subjects (all P > 0.2), although after adjusting for cardiorespiratory fitness, the obese subjects returned significantly higher values than did their normal weight and overweight counterparts (all P < 0.03). However, when expressed with respect to lean mass, the MFO of the normal weight subjects was significantly greater than that of the overweight and obese subjects, independent of age, sex, or cardiorespiratory fitness., Conclusions: Obese individuals have higher absolute MFO values when cardiorespiratory fitness is taken into account, but when expressed with respect to lean mass, normal weight individuals show a greater capacity to oxidize fat during exercise per unit of metabolically active tissue independent of age, sex, or cardiorespiratory fitness. These findings suggest that obese individuals may suffer from metabolic inflexibility during exercise., (Copyright © 2019 Endocrine Society.)

Context: Type 1a and 1b glycogenosis [glycogen storage disorder (GSD)1a, GSD1b] are rare diseases generally associated with malnutrition. Although abnormal substrate oxidation rates and elevated energy expenditures might contribute to malnutrition, this issue has not been investigated., Objective: To investigate whether abnormal resting energy expenditure (REE) and substrate oxidation rate characterize patients with GSD1., Design: Cross-sectional study., Setting: Outpatient referral center for rare diseases and laboratory of clinical nutrition at the University Hospital of Palermo., Patients: Five consecutive patients with GSD1 (4 type a, 1 type b; 3 men, 2 women; age range, 19 to 49 years)., Main Outcome Measures: The usual clinical procedures for patients with malnutrition, including REE and basal substrate oxidation rate (both indirect calorimetry), body composition (bioimpedance method), muscle strength (hand-grip test), and the usual laboratory tests, were performed., Results: Malnutrition was clearly diagnosed in 2 patients (1 GSD1a and 1 GSD1b), with REE elevated in all five patients, and especially, in the two malnourished patients (+124% and +32.1% vs predictive values using Harris-Benedict equations). The two malnourished patients also exhibited lower basal protein oxidation rates (7.7% and 6.6%) than the nourished patients (range, 12.1% to 24.7%), with higher carbohydrate or lipid oxidation rates. Additionally, the two malnourished patients exhibited higher blood concentrations of lactic acid than the nourished patients., Conclusions: According to data obtained from our small sample of patients with GSD1, elevated REEs seem to be a common characteristic that might contribute to malnutrition. Low basal protein oxidation rates and elevated blood lactic acid concentrations appear to be associated with malnutrition., (Copyright © 2019 Endocrine Society.)

Leptin signals to regulate food intake and energy expenditure under conditions of normative energy homeostasis. The central expression and function of leptin receptor B (LepRb) have been extensively studied during the past two decades; however, the mechanisms by which LepRb signaling dysregulation contributes to the pathophysiology of obesity remains unclear. The paraventricular nucleus of the hypothalamus (PVN) plays a crucial role in regulating energy balance as well as the neuroendocrine axes. The role of LepRb expression in the PVN in regard to the regulation of physiological function of leptin has been controversial. The single-minded homolog 1 gene (Sim1) is densely expressed in the PVN and in parts of the amygdala, making Sim1-Cre mice a useful model for examining molecular mechanisms regulating PVN function. In this study, we characterized the physiological role of LepRb in Sim1-expressing neurons using LepRb-floxed × Sim1-Cre mice. Sim1-specific LepRb-deficient mice were surprisingly hypophagic on regular chow but gained more weight upon exposure to a high-fat diet than did their control littermates. We show that Sim1-specific deletion of a single LepRb gene copy caused decreased surface and core body temperatures as well as decreased energy expenditure in ambient room temperatures in both female and male mice. Furthermore, cold-induced adaptive (nonshivering) thermogenesis is disrupted in homozygous knockout mice. A defective thermoregulatory response was associated with defective cold-induced upregulation of uncoupling protein 1 in brown adipose tissue and reduced serum T4. Our study provides novel functional evidence supporting LepRb signaling in Sim1 neurons in the regulation of body weight, core body temperature, and cold-induced adaptive thermogenesis., (Copyright © 2019 Endocrine Society.)

Context: Primary carnitine deficiency (PCD) is an inborn error of fatty acid metabolism. Patients with PCD are risk for sudden heart failure upon fasting or illness if they are not treated with daily l-carnitine., Objective: To investigate energy metabolism during exercise in patients with PCD with and without l-carnitine treatment., Design: Interventional study., Setting: Hospital exercise laboratories and department of cardiology., Participants: Eight adults with PCD who were homozygous for the c.95A>G (p.N32S) mutation and 10 healthy age- and sex-matched controls., Intervention: Four-day pause in l-carnitine treatment., Main Outcome Measures: Total fatty acid and palmitate oxidation rates during 1-hour submaximal cycle ergometer exercise assessed with stable isotope method (U13C-palmitate and 2H2-d-glucose) and indirect calorimetry with and without l-carnitine., Results: Total fatty acid oxidation rate was higher in patients with l-carnitine treatment during exercise than without treatment [12.3 (SD, 3.7) vs 8.5 (SD, 4.6) µmol × kg-1 × min-1; P = 0.008]. However, the fatty acid oxidation rate was still lower in patients treated with l-carnitine than in the healthy controls [29.5 (SD, 10.1) µmol × kg-1 × min-1; P < 0.001] and in the l-carnitine group without treatment it was less than one third of that in the healthy controls (P < 0.001). In line with this, the palmitate oxidation rates during exercise were lower in the no-treatment period [144 (SD, 66) µmol × kg-1 × min-1] than during treatment [204 (SD, 84) µmol × kg-1 × min-1; P = 0.004) ., Conclusions: The results indicate that patients with PCD have limited fat oxidation during exercise. l-Carnitine treatment in asymptomatic patients with PCD may not only prevent cardiac complications but also boost skeletal muscle fat metabolism during exercise.

Context: In healthy adults with detectable cold-induced brown adipose tissue activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined., Objective: To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes., Design, Setting, Participants, and Interventions: Twelve healthy volunteers (seven male and five female) with positive CIBA [>2 standardized uptake value (g/mL)] had 24-hour energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron emission tomography/computed tomography scans were performed after exposure to 16°C for 2 hours to quantify CIBA., Main Outcome Measures: CIBA, 24hEE during EBL, and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 and free T4. Body composition at baseline and 6 months by dual-energy X-ray absorptiometry., Results: Lower urinary norepinephrine and free T4 were associated with higher CIBA (r = -0.65, P = 0.03; and r = -0.75, P < 0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (P = 0.77). Lower CIBA (β = -3.5 kg/standardized uptake value; P < 0.01) predicted fat mass gain, whereas higher urinary norepinephrine and free T4 predicted future fat mass gain at 6 months (β = 3.0 kg per twofold difference in norepinephrine, P = 0.03; and β = 1.2 kg per 0.1-ng/dL difference in free T4, P = 0.03, respectively)., Conclusion: Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain.

Background In the subacute stroke phase, the monitoring of ambulatory activity and activities of daily life with wearable sensors may have relevant clinical applications. Do current commercially available wearable activity trackers allow us to objectively assess the energy expenditure of these activities? The objective of the present study was to compare the energy expenditure evaluated by indirect calorimetry during the course of a scenario consisting of everyday activities while estimating the energy expenditure using several commercialised wearable sensors in post-stroke patients (less than six months since stroke). Method Twenty-four patients (age 68.2 ± 13.9; post-stroke delay 34 ± 25 days) voluntarily participated in this study. Each patient underwent a scenario of various everyday tasks (transfer, walking, etc.). During the implementation, patients wore 14 wearable sensors (Armband, Actigraph GT3X, Actical, pedometer) to obtain an estimate of the energy expenditure. The actual energy expenditure was concurrently determined by indirect calorimetry. Results Except for the Armband worn on the non-plegic side, the results of our study show a significant difference between the energy expenditure values estimated by the various sensors and the actual energy expenditure when the scenario is considered as a whole. Conclusion The present results suggest that, for a series of everyday tasks, the wearable sensors underestimate the actual energy expenditure values in post-stroke patients in the subacute phase and are therefore not accurate. Several factors are likely to confound the results: types of activity, prediction equations, the position of the sensor and the hemiplegia side.

Ames dwarf mice (Prop1 df/df ) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion. Given the unique phenotype of Ames dwarf epididymal WAT, their improved energy metabolism, and lower core body temperature, we hypothesized that Ames dwarf brown adipose tissue (BAT) may function differently from that of their normal littermates. Here we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also use interscapular BAT removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Furthermore, we show that Ames dwarf mice are able to compensate for loss of interscapular BAT by using their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature, and remarkably extended longevity.

Background: Accurate assessment of energy expenditure provides an opportunity to monitor physical activity during cardiac rehabilitation. However, the available assessment methods, based on the combination of heart rate (HR) and body movement data, are not applicable for patients using beta-blocker medication. Therefore, we developed an energy expenditure prediction model for beta-blocker-medicated cardiac rehabilitation patients., Methods: Sixteen male cardiac rehabilitation patients (age: 55.8 ± 7.3 years, weight: 93.1 ± 11.8 kg) underwent a physical activity protocol with 11 low- to moderate-intensity common daily life activities. Energy expenditure was assessed using a portable indirect calorimeter. HR and body movement data were recorded during the protocol using unobtrusive wearable devices. In addition, patients underwent a symptom-limited exercise test and resting metabolic rate assessment. Energy expenditure estimation models were developed using multivariate regression analyses based on HR and body movement data and/or patient characteristics. In addition, a HR-flex model was developed., Results: The model combining HR and body movement data and patient characteristics showed the highest correlation and lowest error (r 2  = 0.84, root mean squared error = 0.834 kcal/minute) with total energy expenditure. The method based on individual calibration data (HR-flex) showed lower accuracy (i 2  = 0.83, root mean squared error = 0.992 kcal/minute)., Conclusions: Our results show that combining HR and body movement data improves the accuracy of energy expenditure prediction models in cardiac patients, similar to methods that have been developed for healthy subjects. The proposed methodology does not require individual calibration and is based on the data that are available in clinical practice., (© The European Society of Cardiology 2016.)

Background: Aerobic interval training (IT) seems to be superior to continuous training (CT) in improving exercise capacity (peak oxygen uptake (VO2)) in coronary artery disease (CAD) patients in some, but not in all studies. Based on theoretical calculations, these comparative studies stated that the energy expenditure (EE) of both programmes is similar. To date, the caloricity of both programmes has never been objectively measured. Therefore, our aim was to objectively measure the EE of the IT and CT programmes described in the protocol of the SAINTEX-CAD study (based on Wisloff et al.; ITw and CTw), and the actually performed training intensities in the SAINTEX-CAD study by Conraads et al. (ITc and CTc)., Methods: Following a two-week run-in period with three IT and three CT training sessions, 18 male CAD patients (mean age 62.4 ± 6.1 years) performed four training sessions in random order on the cycle ergometer: an ITw, CTw, ITc and CTc test session. The EE was assessed by indirect calorimetry using gas exchange measurements obtained with the Oxycon mobile., Results: We found a higher EE for CTc compared to ITc (352 ± 90.8 kcal versus 269 ± 70.7 kcal; p = 0.026), while CTw and ITw seemed to be isocaloric (317 ± 85.2 kcal versus 273 ± 65.3 kcal; p = 0.42). Higher lactate levels were reached after IT sessions (ITw 5.42 ± 1.42 mmol/l, ITc 5.05 ± 1.38 mmol/l) compared to CT sessions (CTw 2.45 ± 1.04 mmol/l, CTc 3.41 ± 1.44 mmol/l) (p < 0.01). Lactate levels increased above baseline levels (1.91 ± 0.34 mmol/l) except for the CTw session., Conclusion: CTc expended significantly more energy compared to ITc, showing that the programmes used in the SAINTEX-CAD study were not isocaloric. In contrast, isocaloricity was met for CTw and ITw., (© The European Society of Cardiology 2016.)

Objective: This study's aim was to evaluate whether the GCKR rs1260326 variant increases hepatic de novo lipogenesis (DNL)., Setting and Design: To test this hypothesis, 14 adolescents, seven homozygous for the common allele (CC) and seven homozygous for the risk allele (TT), underwent measurement of hepatic DNL during the fasting state and after consumption of a carbohydrate (CHO) drink (75 g glucose and 25 g fructose). DNL was assessed through incorporation of deuterium in the palmitate contained in the very low-density lipoprotein., Results: Subjects with TT demonstrated higher fasting fractional DNL (P = .036) and a lower increase in fractional DNL after the CHO challenge (P = .016). With regard to absolute lipogenesis, TT subjects had both higher fasting rates (P = .015) and 44% greater area under the curve of absolute lipogenesis during the study (P = .016), compared to CC subjects. Furthermore, subjects carrying the TT genotype showed higher basal rates of glucose oxidation (P = .0028) and a lower ability than CC subjects to increase the rates of glucose oxidation after the CHO load (P = .054)., Conclusions: This study reports for the first time rates of DNL in obese adolescents and suggests that the GCKR rs1260326 gene variant, which is associated with greater glycolysis, increases hepatic DNL. These data highlight the role of glycolytic carbon flux in liver lipid synthesis and hypertriglyceridemia in these youngsters.

Context: Body fat-free mass (FFM), energy expenditure (EE), and respiratory quotient (RQ) are known predictors of daily food intake. Because FFM largely determines EE, it is unclear whether body composition per se or the underlying metabolism drives dietary intake., Objective: The objective of the study was to test whether 24-hour measures of EE and RQ and their components influence ad libitum food intake independently of FFM., Design and Participants: One hundred seven healthy individuals (62 males/45 females, 84 Native Americans/23 whites; age 33 ± 8 y; body mass index 33 ± 8 kg/m(2); body fat 31% ± 8%) had 24-hour measures of EE in a whole-room indirect calorimeter during energy balance, followed by 3 days of ad libitum food intake using computerized vending machine systems. Body composition was estimated by dual-energy x-ray absorptiometry., Main Outcome Measures: FFM, 24-hour EE, RQ, spontaneous physical activity, sleeping EE (sleeping metabolic rate), awake and fed thermogenesis, and ad libitum food intake (INTAKE) were measured., Results: Higher 24-hour RQ (P < .001, partial R(2) = 16%) and EE (P = .01, partial R(2) = 7%), but not FFM (P = .65), were independent predictors of INTAKE. Mediation analysis demonstrated that 24-hour EE is responsible for 80% of the FFM effect on INTAKE (44.5 ± 16.9 kcal ingested per kilogram of FFM, P= .01), whereas the unique effect due to solely FFM was negligible (10.6 ± 23.2, P = .65). Spontaneous physical activity (r = 0.33, P = .001), but not sleeping metabolic rate (P = .71), positively predicted INTAKE, whereas higher awake and fed thermogenesis determined greater INTAKE only in subjects with a body mass index of 29 kg/m(2) or less (r = 0.44, P = .01)., Conclusions: EE and RQ, rather than FFM, independently determine INTAKE, suggesting that competitive energy-sensing mechanisms driven by the preferential macronutrient oxidation and total energy demands may regulate food intake.

Background: there are no accurate methods for the assessment of food intake in older populations, under-reporting of intake being highly prevalent. There is controversy about which dietary assessment method and what person's characteristics are associated with greater under-reporting rates., Objective: to assess the correlation between under-reporting of energy intake (EI) and different percentages of body fat in independent older people., Design: cross-sectional study., Settting: area assisted by the Family Health Program of the Ribeirão Preto Medical School, University of São Paulo, Brazil., Sujects: one hundred volunteers aged 60-70 years., Methods: all volunteers had their body composition assessed by dual-energy x-ray absorptiometry. In second phase, 41 volunteers were evaluated, representing the four quartiles of fat percentage. Total energy expenditure (TEE) was measured by the doubly labelled water method, and EI was assessed by 24-h recalls and a food frequency questionnaire (FFQ). TEE and EI values, EI-to-TEE ratios and EI-TEE values were compared., Results: TEE was 2,220 ± 601 kcal, while the EI was 1,919 ± 602 kcal (24-h recall) and 2,119 ± 670 kcal (FFQ). The proportion of under-reporters was 31 and 40.5%, respectively. Under-reporting was more frequent in subjects with higher percentage of body fat and in females (P < 0.05)., Conclusion: under-reporting was more frequent among older persons with higher percentage of body fat in both methods of assessment of food intake. Older persons follow the same profile of under-reporting as younger adults., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

During the year 2011, a survey was performed to describe current practices throughout Europe regarding three critical issues of acute burn care, namely fluid resuscitation, nutrition, and burn wound excision strategy. Thirty-eight questionnaires returned by burn centres from 17 different European countries were analyzed. The survey shows that Parkland remains the most commonly used formula to determine fluid needs in adults. All respondent centers use urine output to guide fluid resuscitation. While early excision of deep burns is the rule among centers, burn depth assessment by laser Doppler imaging is used in only a few centers. Indirect calorimetry and Toronto formula to estimate energy requirements do not have unanimous backing from respondents. Current literature encourages clinicians to move forward targeted and individualized therapies using a bundle of basic and advanced hemodynamic parameters, indirect calorimetry, and laser Doppler imaging. The results of this study suggest that such an approach is not common yet, and reinforce the subsequent need for large clinical trials that would evaluate the impact of such guided therapies to provide recommendations with a significant level of evidence.

Context: Oxytocin has been implicated in the modulation of energy metabolism in animals. Oxytocin knockout mice develop obesity without a change in food intake, suggesting that a lack of oxytocin may reduce metabolic rate. Furthermore, administration of oxytocin centrally reduces food intake in rats, an effect reversed by an oxytocin antagonist, implying that oxytocin may regulate appetite and energy intake. We have previously demonstrated that young female athletes (in a higher energy expenditure state than nonathletes) have low nocturnal oxytocin compared with nonathletes. Whether oxytocin is associated with measures of energy homeostasis in athletes is unknown., Objective: We hypothesized that oxytocin, a signal for energy availability, would be associated with other measures of energy homeostasis in young female athletes., Design and Setting: We performed a cross-sectional study of 45 females, aged 14-21 years [15 amenorrheic athletes (AA), 15 eumenorrheic athletes, and 15 nonathletes] of comparable body mass index., Methods: Dual x-ray absorptiometry was performed to assess body composition. Indirect calorimetry was used to measure resting energy expenditure (REE). Fasting levels of oxytocin, energy homeostasis hormones irisin and fibroblast growth factor-21, and appetite-regulating hormone peptide YY were obtained., Results: In AA, oxytocin secretion was positively correlated with surrogate measures of energy availability, including weight (r = 0.65, P = .009) and body mass index (r = 0.61, P = .016). Furthermore, oxytocin was associated with REE (r = 0.80, P = .0003), independent of lean mass, and with irisin (r = 0.74, P = .002) and fibroblast growth factor-21 (r = 0.58, P = .024). In eumenorrheic athletes, oxytocin was associated with REE (r = 0.59, P = .021), independent of lean mass. In nonathletes, oxytocin secretion was not significantly associated with measures of energy homeostasis., Conclusions: In AA, oxytocin secretion is associated with measures of energy availability and expenditure, suggesting that oxytocin may be involved in regulation of energy balance in energy deficient states. Further studies determining the role of oxytocin in appetite and energy homeostasis in athletes are warranted.

Context: Disruption of the Gsα maternal allele leads to severe obesity and insulin resistance in mice and early-onset obesity in patients with pseudohypoparathyroidism (PHP) type 1a. However, insulin resistance and glucose metabolism have not been systematically characterized in patients with PHP1a., Objective, Design, and Setting: In a cross-sectional, case-control study, we examined insulin sensitivity, β-cell function, energy expenditure (EE), and sympathetic nervous system activity in adults with PHP1a., Study Participants: PHP1a patients (n = 8) and healthy control subjects (n = 24) matched for age (41 ± 7 vs 41 ± 7 years [mean ± SD]), gender, and percent body fat., Methods: Insulin sensitivity (SI), acute insulin response to glucose, and disposition index were assessed during a frequently sampled iv glucose tolerance test. Oral glucose insulin sensitivity (OGIS) was measured during a mixed meal. EE was measured using whole-room indirect calorimetry. Body composition was assessed via dual-energy x-ray absorptiometry and sympathetic nervous system activity by measuring 24-hour urinary catecholamine concentrations., Results: PHP1a patients were less insulin-sensitive than their matched controls based upon SI and OGIS. Nondiabetic PHP1a patients tended to have a lower SI (P = .09) and reduced OGIS (P = .03). Disposition index, a composite measure of β-cell function, also tended to be lower in patients (P = .07). Total caloric intake, resting EE, total EE, meal-induced thermogenesis, and 24-hour urinary catecholamine concentrations were not significantly different between the groups., Conclusions: Adults with PHP-1a have reduced insulin sensitivity compared with their matched controls that may contribute to the pathogenesis of glucose intolerance and diabetes in these patients.

Context: The mechanisms of weight loss after Roux-en-Y gastric bypass (RYGB) surgery are incompletely understood., Objective: Our objective was to investigate changes in metabolic processing of ingested food that may contribute to the weight-reducing effect of RYGB surgery., Design and Setting: This was a cross-sectional case-control study at the Interdisciplinary Obesity Center, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Patients: Ten formerly obese women (mean ± SEM body mass index [BMI] = 26.6 ± 0.9 kg/m(2)) who had undergone RYGB surgery 41.9 ± 9.7 months before, 8 severely obese women (BMI = 40.8 ± 2.0 kg/m(2)), and 10 lean women (BMI = 20.9 ± 0.6 kg/m(2))., Intervention: Intervention was a standardized liquid meal test., Main Outcome: The thermic effect of food (TEF), respiratory quotient, and circulating levels of glucose, insulin, and C-peptide were assessed before and repeatedly during the first 90 minutes after the ingestion of a standardized liquid mixed meal containing 39.2 g carbohydrates, 15.4 g protein, and 2.8 g fat., Results: TEF area under curve (0-90 minutes) was significantly greater in RYGB patients than in severely obese and lean women (both P < .01). After ingestion of the mixed meal, the respiratory quotient increased to significantly greater values in the RYGB patients than in the severely obese and lean group (P < .001 for ANOVA time × group interaction). Also, the postprandial rise in circulating glucose, insulin, and C-peptide levels was remarkably higher in the RYGB patients than in the other 2 groups (all P < .001 for ANOVA time × group interaction)., Conclusion: Data demonstrate an enhanced TEF after RYGB surgery. Although this observation likely contributes to the weight-reducing effects of the surgery, data also point to an altered metabolic processing of food in RYGB patients characterized by an enhanced glucose absorption and postprandial carbohydrate oxidation.

Context: Individual variation in the ability to convert excess calories to heat and the effects of dietary macronutrient composition are unclear., Objective: Stability and determinants of the energy expenditure (EE) response to overconsumption were assessed., Design, Setting, and Participants: Twenty subjects (75% male) with normal glucose regulation were evaluated during 24 hours each of energy balance, fasting, and 5 different diets with 200% energy requirements in a clinical research unit., Interventions: Five 1-day overfeeding diets were given in random order: high carbohydrate (75%) and low protein (3%); high carbohydrate and normal protein (20%); high fat (46%) and low protein; high fat (60%) and normal protein; and balanced (50% carbohydrates, 20% protein)., Main Outcome Measures: The 24-hour EE, sleeping EE, and thermic effect of food (TEF) during each diet were measured with a metabolic chamber. Appetitive hormones were measured before and after the diets., Results: The EE response to overfeeding exhibited good intraindividual reproducibility. Similar increases above eucaloric feeding in 24-hour EE (mean 10.7 ± 5.7%, P < .001; range 2.9-18.8%) and sleeping EE (14.4 ± 11.3%, P < .001; range 1.0-45.1%) occurred when overfeeding diets containing 20% protein, despite differences in fat and carbohydrate content, but the EE response during overfeeding diets containing 3% protein was attenuated. The percent body fat negatively correlated with TEF during normal protein overfeeding (r = -0.53, P < .01). Fasting peptide YY negatively correlated with TEF (r = -0.56, P < .01) and the increase in sleeping EE (r = -0.54, P < .01) during overfeeding., Conclusions: There is an intrinsic EE response to overfeeding that negatively associates with adiposity, although it represents a small percentage of consumed calories.

Context: The contribution of brown adipose tissue (BAT) to the energy balance in humans exposed to sustainable cold has not been completely established, partially because of measurement limitations of both BAT activity and energy expenditure (EE)., Objective: The objective of the study was to characterize the role of BAT activation in cold-induced thermogenesis (CIT)., Design: This study was a single-blind, randomized crossover intervention., Setting: The study was conducted at the National Institutes of Health Clinical Center., Study Participants: Thirty-one healthy volunteers participated in the study., Interventions: The intervention included mild cold exposure., Main Outcomes: CIT and BAT activation were the main outcomes in this study., Methods: Overnight EE measurement by whole-room indirect calorimeter at 24 °C or 19 °C was followed by 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan. After 36 hours, volunteers crossed over to the alternate study temperature under identical conditions. BAT activity was measured in a 3-dimensional region of interest in the upper torso by comparing the uptake at the two temperatures., Results: Twenty-four volunteers (14 males, 10 females) had a complete data set. When compared with 24 °C, exposure at 19 °C resulted in increased EE (5.3 ± 5.9%, P < .001), indicating CIT response and mean BAT activity (10.5 ± 11.1%, P < .001). Multiple regression analysis indicated that a difference in BAT activity (P < .001), age (P = .01), and gender (P = .037) were independent contributors to individual variability of CIT., Conclusions: A small reduction in ambient temperature, within the range of climate-controlled buildings, is sufficient to increase human BAT activity, which correlates with individual CIT response. This study uncovers for the first time a spectrum of BAT activation among healthy adults during mild cold exposure not previously recognized by conventional PET and PET-computed tomography methods. The enhancement of cold-induced BAT stimulation may represent a novel environmental strategy in obesity treatment.

Context: The relevance of the contribution of energy expenditure (EE) and substrate oxidation to weight change has not been fully confirmed., Objective: The objective of the study was to determine whether metabolic parameters measured in a whole room indirect calorimeter are predictive of long-term body weight change., Setting: The study was conducted at a clinical research unit in Phoenix, Arizona, from 1985 to 2005., Participants: A total of 612 healthy subjects (384 males and 228 females; aged 29.5 ± 8.1 years; body mass index 33.0 ± 8.7 kg/m(2); percent body fat 30.9 ± 9.6%), including 422 Native Americans and 190 whites. Follow-up data were available for 292 Native Americans with a median follow-up time of 6.7 years (interquartile range 3.9-10.5)., Main Outcome Measures: Twenty-four-hour EE, sleeping metabolic rate, daily (fed) and sleeping (fasting) respiratory quotient, and carbohydrate and fat oxidation rates were measured during a 24-hour respiratory chamber. Body composition was assessed by underwater weighing or dual-energy x-ray absorptiometry., Results: After accounting for demographic and body composition measures, the remaining variance of 24-hour EE was inversely related to the rate of weight change (ρ = -0.158, P = .007) and fat mass change (ρ = -0.179, P = .012), such that 100 kcal below the expected 24-hour EE corresponded to 0.2 kg/y weight gain, of which 0.1 kg/y was fat mass. Deviations from the predicted values of the sleeping metabolic rate (ρ = -0.121, P = .039) and fed respiratory quotient (ρ = 0.119, P = .042) were also associated with future weight change, whereas the fat oxidation rate was inversely associated with weight change in men (ρ = -0.174, P = .024) but not in women (ρ = 0.018, P = .853)., Conclusions: Measures of energy expenditure and substrate oxidation are predictors of long-term weight change, indicating a small but significant role for reduced metabolic rate in weight gain.

We used a biomarker of activity-related energy expenditure (AREE) to assess measurement properties of self-reported physical activity and to determine the usefulness of AREE regression calibration equations in the Women's Health Initiative. Biomarker AREE, calculated as the total energy expenditure from doubly labeled water minus the resting energy expenditure from indirect calorimetry, was assessed in 450 Women's Health Initiative participants (2007-2009). Self-reported AREE was obtained from the Arizona Activity Frequency Questionnaire (AAFQ), the 7-Day Physical Activity Recall (PAR), and the Women's Health Initiative Personal Habits Questionnaire (PHQ). Eighty-eight participants repeated the protocol 6 months later. Reporting error, measured as log(self-report AREE) minus log(biomarker AREE), was regressed on participant characteristics for each instrument. Body mass index was associated with underreporting on the AAFQ and PHQ but overreporting on PAR. Blacks and Hispanics underreported physical activity levels on the AAFQ and PAR, respectively. Underreporting decreased with age for the PAR and PHQ. Regressing logbiomarker AREE on logself-reported AREE revealed that self-report alone explained minimal biomarker variance (R(2) = 7.6, 4.8, and 3.4 for AAFQ, PAR, and PHQ, respectively). R(2) increased to 25.2, 21.5, and 21.8, respectively, when participant characteristics were included. Six-month repeatability data adjusted for temporal biomarker variation, improving R(2) to 79.4, 67.8, and 68.7 for AAFQ, PAR, and PHQ, respectively. Calibration equations "recover" substantial variation in average AREE and valuably enhance AREE self-assessment.

Background: Brown adipose tissue (BAT) was considered essentially nonexistent in adults until recent evidence obtained using 18-fluorodeoxyglucose (18-FDG) positron emission tomography/computed tomography. It seems to play a role in whole body metabolism, but it has not been evaluated in underweight conditions, such as in young females with constitutional leanness (CL) or anorexia nervosa (AN)., Subjects and Methods: Thirty-eight subjects were evaluated from October 2011 to March 2012 : 7 CL (21.7 ± 3.6 y, body mass index [BMI] 16.2 ± 1.0 kg/m(2)), 7 AN (23.4 ± 4.5 y, BMI 15.5 ± 0.8), 3 of the 7 AN after stable refeeding (R-AN, 21.3 ± 1.5 y, BMI 18.8 ± 1.1), and 24 normal weight (NW) women (25.6 ± 3.9 y, BMI 22.2 ± 1.5). Fasting resting metabolic rate and respiratory quotient were measured by indirect calorimetry, body composition by bioimpedentiometry (only in CL, AN, and refed AN), and BAT activity by 18-FDG positron emission tomography/computed tomography scan, all in standardized conditions., Results: All CL (100%), none of the AN and refed AN (0%), and 3 of the 24 NW (12%) subjects showed FDG uptake. Average FDG maximum standardized uptake value was 11.4 + 6.7 g/mL in CL and 5.5 ± 1.2 g/mL (min 3.7, max 8.3) in the 3 NW subjects. In CL, the maximum standardized uptake value was directly correlated to resting metabolic rate, corrected for fat-free mass, and inversely correlated with respiratory quotient., Conclusion: BAT activity has been shown in CL in resting thermoneutral conditions and may exert a role against adipose tissue deposition.

Long-term ingestion of coffee polyphenols (chlorogenic acids, CGAs) reduces body fat in humans and rodents. While CGA supplementation has been shown to increase fat utilization in rodents, evidence in humans is still limited. The present study clarifies the effect of daily CGA consumption on energy metabolism in humans. Eighteen healthy male subjects (36.1 ± 7.4 y of age) participated in a placebo-controlled, double-blind, crossover, intervention study with two different test beverages. The subjects consumed 185 mL of a test beverage with or without CGAs (329 mg) daily for 4 wk. The energy metabolism was evaluated by using indirect calorimetry before and after the test period during fasting and up to 180 min postprandially. Indirect calorimetry showed that a 4-wk ingestion of the CGA beverage led to a significantly higher postprandial energy expenditure than that of the control beverage. The subjects ingesting the CGA beverage exhibited higher postprandial fat utilization than those consuming the control beverage. The daily CGA consumption therefore increased postprandial fat utilization in healthy humans.

Cannabinoid type 1 (CB(1)) receptor activation is generally considered a powerful orexigenic signal and inhibition of the endocannabinoid system is beneficial for the treatment of obesity and related metabolic diseases. The hypothalamus plays a critical role in regulating energy balance by modulating both food intake and energy expenditure. Although CB(1) receptor signaling has been implicated in the modulation of both these mechanisms, a complete understanding of its role in the hypothalamus is still lacking. Here we combined a genetic approach with the use of adeno-associated viral vectors to delete the CB(1) receptor gene in the adult mouse hypothalamus and assessed the impact of such manipulation on the regulation of energy balance. Viral-mediated deletion of the CB(1) receptor gene in the hypothalamus led to the generation of Hyp-CB(1)-KO mice, which displayed an approximately 60% decrease in hypothalamic CB(1) receptor mRNA levels. Hyp-CB(1)-KO mice maintained on a normocaloric, standard diet showed decreased body weight gain over time, which was associated with increased energy expenditure and elevated β(3)-adrenergic receptor and uncoupling protein-1 mRNA levels in the brown adipose tissue but, surprisingly, not to changes in food intake. Additionally, Hyp-CB(1)-KO mice were insensitive to the anorectic action of the hormone leptin (5 mg/kg) and displayed a time-dependent hypophagic response to the CB(1) inverse agonist rimonabant (3 mg/kg). Altogether these findings suggest that hypothalamic CB(1) receptor signaling is a key determinant of energy expenditure under basal conditions and reveal its specific role in conveying the effects of leptin and pharmacological CB1 receptor antagonism on food intake.

Intrauterine growth restriction (IUGR) results in dysregulated glucose homeostasis and adiposity in the adult. We hypothesized that with aging, these perturbations will wane, and superimposition of postnatal growth restriction (PNGR) on IUGR [intrauterine and postnatal growth restriction (IPGR)] will reverse the residual IUGR phenotype. We therefore undertook hyperinsulinemic-euglycemic clamp, energy balance, and physical activity studies during fed, fasted, and refed states, in light and dark cycles, on postweaned chow diet-fed more than 17-month aging male IUGR, PNGR, and IPGR vs. control (CON) rat offspring. Hyperinsulinemic-euglycemic clamp revealed similar whole-body insulin sensitivity and physical activity in the nonobese IUGR vs. CON, despite reduced heat production and energy expenditure. Compared with CON and IUGR, IPGR mimicking PNGR was lean and growth restricted with increased physical activity, O(2) consumption (VO(2)), energy intake, and expenditure. Although insulin sensitivity was no different in IPGR and PNGR, skeletal muscle insulin-induced glucose uptake was enhanced. This presentation proved protective against the chronologically earlier (5.5 months) development of obesity and dysregulated energy homeostasis after 19 wk on a postweaned high-fat diet. This protective role of PNGR on the metabolic IUGR phenotype needs future fine tuning aimed at minimizing unintended consequences.

Context: Reduction of 50% excess body weight, using a very low-calorie diet (VLCD; 450 kcal/d) improves insulin sensitivity in obese type 2 diabetes mellitus patients., Objective: The objective of the study was to evaluate whether adding exercise to the VLCD has additional benefits., Design: This was a randomized intervention study., Setting: The study was conducted at a clinical research center in an academic medical center., Subjects: Twenty-seven obese [body mass index 37.2 ± 0.9 kg/m(2) (mean ± sem)] insulin-treated type 2 diabetes mellitus patients., Intervention: Patients followed a 16-wk VLCD. Thirteen of them simultaneously participated in an exercise program (E) consisting of 1-h, in-hospital training and four 30-min training sessions on a cycloergometer weekly., Outcome Measures: Insulin resistance was measured by a hyperinsulinemic euglycemic clamp. Insulin signaling, mitochondrial DNA (mtDNA) content, and intramyocellular lipid content was measured in skeletal muscle biopsies., Results: Baseline characteristics were identical in both groups. Substantial weight loss occurred (-23.7 ± 1.7 kg VLCD-only vs. -27.2 ± 1.9 kg VLCD+E, P = NS within groups). The exercise group lost more fat mass. Insulin-stimulated glucose disposal increased similarly in both study groups [15.0 ± 0.9 to 39.2 ± 4.7 μmol/min(-1) · kg lean body mass (LBM(-1)) VLCD-only vs. 17.0 ± 1.0 to 37.5 ± 3.5 μmol/min(-1) · kg LBM(-1) in VLCD+E], as did phosphorylation of the phosphatidylinositol 3-kinase-protein kinase B/AKT insulin signaling pathway. In contrast, skeletal muscle mtDNA content increased only in the VLCD+E group (1211 ± 185 to 2288 ± 358, arbitrary units, P = 0.016 vs. 1397 ± 240 to 1196 ± 179, P = NS, VLCD-only group). Maximum aerobic capacity also only increased significantly in the VLCD+E group (+6.6 ± 1.7 ml/min(-1) · kg LBM(-1) vs. +0.7 ± 1.5 ml/min(-1) · kg LBM(-1) VLCD-only, P = 0.017)., Conclusion: Addition of exercise to a 16-wk VLCD induces more fat loss. Exercise augments maximum aerobic capacity and skeletal muscle mtDNA content. These changes are, however, not reflected in a higher insulin-stimulated glucose disposal rate.