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Purpose To investigate the association of meal timing with body composition and cardiometabolic risk factors in young adults. Methods In this cross-sectional study participated 118 young adults (82 women; 22 ± 2 years old; BMI: 25.1 ± 4.6 kg/m2). Meal timing was determined via three non-consecutive 24-h dietary recalls. Sleep outcomes were objectively assessed using accelerometry. The eating window (time between first and last caloric intake), caloric midpoint (local time at which ≥ 50% of daily calories are consumed), eating jetlag (variability of the eating midpoint between non-working and working days), time from the midsleep point to first food intake, and time from last food intake to midsleep point were calculated. Body composition was determined by DXA. Blood pressure and fasting cardiometabolic risk factors (i.e., triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and insulin resistance) were measured. Results Meal timing was not associated with body composition (p > 0.05). The eating window was negatively related to HOMA-IR and cardiometabolic risk score in men (R2 = 0.348, β = − 0.605; R2 = 0.234, β = − 0.508; all p ≤ 0.003). The time from midsleep point to first food intake was positively related to HOMA-IR and cardiometabolic risk score in men (R2 = 0.212, β = 0.485; R2 = 0.228, β = 0.502; all p = 0.003). These associations remained after adjusting for confounders and multiplicity (all p ≤ 0.011). Conclusions Meal timing seems unrelated to body composition in young adults. However, a longer daily eating window and a shorter time from midsleep point to first food intake (i.e., earlier first food intake in a 24 h cycle) are associated with better cardiometabolic health in young men. Clinical trial registration NCT02365129 (https://www.clinicaltrials.gov/ct2/show/NCT02365129?term=ACTIBATE&draw=2&rank=1).

Purpose Thyroid hormones (THs) are important mediators of brown adipose tissue (BAT) differentiation. However, the association of TH concentrations with human BAT is unclear. The present work examines the associations between circulating thyroid-stimulating hormone (TSH) and THs concentrations (i.e. free triiodothyronine, FT3, and free thyroxine, FT4), under thermoneutral (22–23°C) and cold-induced conditions, and BAT volume, 18F-fluorodeoxyglucose (18F-FDG) uptake and mean radiodensity. Methods A total of 106 young healthy, euthyroid adults (34 men/72 women; 22.0 ± 2.1 years old; 24.9 ± 4.6 kg/m2) participated in this cross-sectional study. BAT volume, 18F-FDG uptake and mean radiodensity were assessed after 2 h of personalized (i.e. contemplating each individual's shivering threshold) cold exposure via positron emission tomography/computed tomography (PET/CT) static scanning. TSH and THs levels were determined before (thermoneutral) and 1 h after the cold exposure. Results Cold exposure increased circulating FT4 (P = 0.038) and reduced TSH levels (P ≤ 0.001). Conversely, the FT3 serum concentration was not modified by cold exposure (P = 0.435). No associations were found between the TSH and THs thermoneutral (all P > 0.111) or cold-induced levels (all P > 0.067) and BAT volume, 18F-FDG uptake and mean radiodensity. These findings were independent of sex and BMI. Conclusions Thyroid function is modulated by cold exposure, yet it is not associated with BAT volume or glucose metabolism assessed after 2 h of cold exposure in young healthy, euthyroid adults.

Purpose Metabolic flexibility (MetF), which is a surrogate of metabolic health, can be assessed by the change in the respiratory exchange ratio (RER) in response to an oral glucose tolerance test (OGTT). We aimed to determine the day-to-day reproducibility of the energy expenditure (EE) and RER response to an OGTT, and whether a simulation-based postcalorimetric correction of metabolic cart readouts improves day-to-day reproducibility. Methods The EE was assessed (12 young adults, 6 women, 27 ± 2 years old) using an Omnical metabolic cart (Maastricht Instruments, Maastricht, The Netherlands) after an overnight fast (12 h) and after a 75-g oral glucose dose on 2 separate days (48 h). On both days, we assessed EE in 7 periods (one 30-min baseline and six 15-min postprandial). The ICcE was performed immediately after each recording period, and capillary glucose concentration (using a digital glucometer) was determined. Results We observed a high day-to-day reproducibility for the assessed RER (coefficients of variation [CV] < 4%) and EE (CVs < 9%) in the 7 different periods. In contrast, the RER and EE areas under the curve showed a low day-to-day reproducibility (CV = 22% and 56%, respectively). Contrary to our expectations, the postcalorimetric correction procedure did not influence the day-to-day reproducibility of the energy metabolism response, possibly because the Omnical’s accuracy was ~ 100%. Conclusion Our study demonstrates that the energy metabolism response to an OGTT is poorly reproducible (CVs > 20%) even using a very accurate metabolic cart. Furthermore, the postcalorimetric correction procedure did not influence the day-to-day reproducibility., Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad grant DEP2016-79512-R, European Commission, Spanish Government FPU15/04059 FPU19/01609, University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health, Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades via the ERDF SOMM17/6107/UGR, Fundacion Alfonso Martin Escudero, Universidad de Granada/CBUA

Purpose: Brown adipose tissue (BAT) increases metabolic heat production in response to cold exposure. Body size and composition are involved in the human cold response, yet the influence of BAT herein have not fully been explored. Here, we aimed to study the association of the cold-induced shivering threshold time with body composition, BAT, the perception of shivering and skin temperature in young adults. Methods: 110 young healthy adults (81 females; age = 21.7 ± 2.1 years, BMI = 24.2 ± 4.3 kg/m2) underwent 2 h of individualized cooling, followed by the quantification of BAT using a18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography-computed tomography (PET-CT) scan. Body mass index (BMI), lean mass, fat mass and body surface area (BSA) were also measured. Shivering threshold time was defined as the time until shivering occurred using an individualized cooling protocol. Results: The shivering threshold time was on average 116.1 min for males and 125.8 min for females, and was positively associated to BMI (β = 3.106; R2 = 0.141; p = 0.001), lean mass (β = 2.295; R2 = 0.128; p = 0.001) and fat mass (β = 1.492; R2 = 0.121; p = 0.001) in females, but not in males (all p ≥ 0.409). The shivering threshold time was positively associated with BSA in males (p = 0.047) and females (p = 0.001), but it was not associated with BAT volume or [18F]FDG uptake nor with the perception of shivering and skin temperature perception in both sexes. Conclusion: The shivering threshold time is positively associated with whole-body adiposity and lean mass in females, but not in males. The shivering threshold time was positively associated with BSA, but no association was observed with BAT nor with the perception of shivering or skin temperature. Future research should consider the influence of body composition when applying cooling protocols among individuals with different phenotypical features., Spanish Government PI13/01393 PTA 12264-I, Retos de la Sociedad DEP 2016-79512-R, European Commission, Spanish Government FPU 13/03410, Fundacion Iberoamericana de Nutricion (FINUT), Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022, AstraZeneca, University of Granada Plan Propio de Investigacion 2016 - Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Plan Propio de Investigacion 2018: Programa ContratosPuente, Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR, Fundacion Carolina C.2016-574,961, Fundacion Alfonso Martin Escudero, Ministerio de Universidades y la Union Europea-NextGenerationEU RR_C_2021_04

The present work examines the relationships between maximal fat oxidation during a graded exercise test (MFO), the intensity of exercise that elicits MFO (Fatmax), and traditional cardiometabolic r...

Metabolic flexibility (MetF), which is a surrogate of metabolic health, can be assessed by the change in the respiratory exchange ratio (RER) in response to an oral glucose tolerance test (OGTT). We aimed to determine the day-to-day reproducibility of the energy expenditure (EE) and RER response to an OGTT, and whether a simulation-based postcalorimetric correction of metabolic cart readouts improves day-to-day reproducibility.The EE was assessed (12 young adults, 6 women, 27 ± 2 years old) using an Omnical metabolic cart (Maastricht Instruments, Maastricht, The Netherlands) after an overnight fast (12 h) and after a 75-g oral glucose dose on 2 separate days (48 h). On both days, we assessed EE in 7 periods (one 30-min baseline and six 15-min postprandial). The ICcE was performed immediately after each recording period, and capillary glucose concentration (using a digital glucometer) was determined.We observed a high day-to-day reproducibility for the assessed RER (coefficients of variation [CV] 4%) and EE (CVs 9%) in the 7 different periods. In contrast, the RER and EE areas under the curve showed a low day-to-day reproducibility (CV = 22% and 56%, respectively). Contrary to our expectations, the postcalorimetric correction procedure did not influence the day-to-day reproducibility of the energy metabolism response, possibly because the Omnical's accuracy was ~ 100%.Our study demonstrates that the energy metabolism response to an OGTT is poorly reproducible (CVs 20%) even using a very accurate metabolic cart. Furthermore, the postcalorimetric correction procedure did not influence the day-to-day reproducibility. Trial registration NCT04320433; March 25, 2020.

In rodents, exercise alters the plasma concentration of exerkines that regulate white adipose tissue (WAT) browning or brown adipose tissue (BAT) metabolism. This study aims to analyse the acute and chronic effect of exercise on the circulating concentrations of 16 of these exerkines in humans. Ten young sedentary adults (6 female) performed a maximum walking effort test and a resistance exercise session. The plasma concentration of 16 exerkines was assessed before, and 3, 30, 60, and 120 min after exercise. Those exerkines modified by exercise were additionally measured in another 28 subjects (22 women). We also measured the plasma concentrations of the exerkines before and after a 24-week exercise programme (endurance + resistance; 3-groups: control, moderate-intensity and vigorous-intensity) in 110 subjects (75 women). Endurance exercise acutely increased the plasma concentration of lactate, norepinephrine, brain-derived neurotrophic factor, interleukin 6, and follistatin-like protein 1 (3 min after exercise), and musclin and fibroblast growth factor 21 (30 and 60 min after exercise), decreasing the plasma concentration of leptin (30 min after exercise). Adiponectin, atrial natriuretic peptide (ANP), beta-aminoisobutyric acid, meteorin-like, follistatin, pro-ANP, irisin and myostatin were not modified or not detectable. The resistance exercise session increased the plasma concentration of lactate 3 min after exercise. Chronic exercise did not alter the plasma concentration of these exerkines. In sedentary young adults, acute endurance exercise releases to the bloodstream exerkines that regulate BAT metabolism and WAT browning. In contrast, neither a low-volume resistance exercise session nor a 24-week training programme modified plasma levels of these molecules.

Funding for open access charge: Universidad de Granada/CBUA. This study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393), by the Retos de la Sociedad program (DEP2016-79512-R), European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU13/04365), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas de Investigacion Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)-and Plan Propio de Investigacion 2018-the Programa Contratos-Puente and Contratos Perfeccionamiento de Doctores, the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF; ref. SOMM17/6107/UGR), and the Fundacion Alfonso Martin Escudero (grant awarded to GSD)., Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129., Universidad de Granada/CBUA, Spanish Government PI13/01393, Retos de la Sociedad program DEP2016-79512-R, European Commission, Spanish Government FPU13/04365, Fundacion Iberoamericana de Nutricion (FINUT), Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022, AstraZeneca, University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Plan Propio de Investigacion 2018-the Programa Contratos-Puente, Contratos Perfeccionamiento de Doctores, Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR, Fundacion Alfonso Martin Escudero

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.

Supported by the Spanish Ministry of Economy and Competitiveness via Fondo de Investigación Sanitaria del Instituto de Salud Carlos III grant PI13/01393 (to JRR), Retos de la Sociedad grant DEP2016-79512-R (to JRR), and European Regional Development Funds (ERDF); Spanish Ministry of Education grant FPU13/04365 (to GS-D); the Fundación Iberoamericana de Nutrición (to JRR); Redes Temáticas de Investigación Cooperativa grant Red SAMID RD16/0022 (to AG); the AstraZeneca HealthCare Foundation; the University of Granada Plan Propio de Investigación 2016—Excellence actions:Unit of Excellence on Exercise and Health (to JRR)—and Plan Propio de Investigación 2018—Programa Contratos-Puente (to GS-D); and Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidadesgrant SOMM17/6107/UGR (to JRR) via the ERDF., Background: Several studies have explored the role of human brown adipose tissue (BAT) in energy expenditure. However, the link between BAT and appetite regulation needs to be more rigorously examined. Objective: We aimed to investigate the associations of BAT volume and 18F-fluordeoxyglucose (18F-FDG) uptake after a personalized cold exposure with energy intake and appetite-related sensations in young healthy humans. Methods: A total of 102 young adults (65 women; age: 22.08 ± 2.17 y; BMI: 25.05 ± 4.93 kg/m 2) took part in this cross-sectional study. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18FFDG uptake were assessed by means of static 18F-FDG positronemission tomography and computed tomography scans after a 2-h personalized exposure to cold. Energy intake was estimated via an objectively measured ad libitum meal and three nonconsecutive 24-h dietary recalls. Appetite-related sensations (i.e., hunger and fullness) were recorded by visual analog scales before and after a standardized breakfast (energy content = 50% of basal metabolic rate) and the ad libitum meal. Body composition was assessed by a whole-body DXA scan. Results: BAT volume and 18F-FDG uptake were not associated with quantified ad libitum energy intake (all P > 0.088), nor with habitual energy intake estimated from the 24-h dietary recalls (all P > 0.683). Lean mass was positively associated with both the energy intake from the ad libitum meal (β: 17.612, R2 = 0.213; P < 0.001) and the habitual energy intake (β: 16.052, R2 = 0.123; P = 0.001). Neither the interaction BAT volume × time elapsed after meal consumption nor that of BAT 18F-FDG uptake × time elapsed after meal consumption had any significant influence on appetite-related sensations after breakfast or after meal consumption (all P > 0.3). Conclusions: Neither BAT volume, nor BAT 18F-FDG uptake after cold stimulation, are related to appetite regulation in young adults. These results suggest BAT plays no important role in the regulation of energy intake in humans. This trial was registered at clinicaltrials.gov as NCT02365129., Fondo de Investigación Sanitaria del Instituto de Salud Carlos III grant PI13/01393 (to JRR), Retos de la Sociedad grant DEP2016-79512-R (to JRR), Redes Temáticas de Investigación Cooperativa grant Red SAMID RD16/0022 (to AG), Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidadesgrant SOMM17/6107/UGR (to JRR) via the ERDF.

This cross-sectional study investigates the relationship between the shed form of the Klotho protein (S-Klotho) in plasma, and cardiometabolic risk in healthy, sedentary adults. The study subjects were 214 healthy, sedentary adults (~64% women). Data were collected during the baseline assessments of two randomized controlled trials: The FIT-AGEING study (n=74 [~50% women] middle-aged adults aged 40-65 years) and the ACTIBATE study (n=140 [~70% women] young adults aged 18-25 years). A sex-specific cardiometabolic risk score was calculated for each subject based on waist circumference, systolic and diastolic blood pressure, and plasma glucose, high-density lipoprotein cholesterol and triglycerides. A significant inverse relationship was detected between S-Klotho and the cardiometabolic risk score of both the middle-aged men and women (β=-0.658, R2=0.433, P0.5), nor for the young, healthy men and women when analysed separately (all P>0.1). In conclusion, in healthy, sedentary, middle-aged adults, but not in young, healthy, sedentary adults, higher plasma S-Klotho concentrations are associated with a lower cardiometabolic risk score.

Objectives Brown adipose tissue (BAT) is important in the maintenance of cardiometabolic health in rodents. Recent reports appear to suggest the same in humans, although if this is true remains elusive partly because of the methodological bias that affected previous research. This cross-sectional work reports the relationships of cold-induced BAT volume, activity (peak standardized uptake, SUVpeak), and mean radiodensity (an inverse proxy of the triacylglycerols content) with the cardiometabolic and inflammatory profile of 131 young adults, and how these relationships are influenced by sex and body weight. Design This is a cross-sectional study. Methods Subjects underwent personalized cold exposure for 2 h to activate BAT, followed by static 18F-fluorodeoxyglucose PET-CT scanning to determine BAT variables. Information on cardiometabolic risk (CMR) and inflammatory markers was gathered, and a CMR score and fatty liver index (FLI) were calculated. Results In men, BAT volume was positively related to homocysteine and liver damage markers concentrations (independently of BMI and seasonality) and the FLI (all P ≤ 0.05). In men, BAT mean radiodensity was negatively related to the glucose and insulin concentrations, alanine aminotransferase activity, insulin resistance, total cholesterol/HDL-C, LDL-C/HDL-C, the CMR score, and the FLI (all P ≤ 0.02). In women, it was only negatively related to the FLI (P < 0.001). These associations were driven by the results for the overweight and obese subjects. No relationship was seen between BAT and inflammatory markers (P > 0.05). Conclusions A larger BAT volume and a lower BAT mean radiodensity are related to a higher CMR, especially in young men, which may support that BAT acts as a compensatory organ in states of metabolic disruption.

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.

This study was funded 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, and by Retos de la Sociedad (DEP2016-79512-R) and European Regional Development Fund, the Spanish Ministry of Education (FPU 13/03410, FPU 15/04059), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas de Investigaci on Cooperativa RETIC network (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, The University of Granada's Plan Propio de Investigacion 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES), the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF, SOMM17/6107/UGR), and the Fundacion Alfonso Martin Escudero. This study is part of a PhD thesis conducted within the framework of the Biomedicine Doctoral Studies Programme of the University of Granada, Spain., Background: Harnessing cold-induced thermogenesis (CIT) and brown adipose tissue (BAT) activity has been proposed as a means of counteracting a positive energy balance, and thus of combating obesity and its related comorbidities. However, it has remained unclear whether CIT and BAT activity show diurnal variation in humans - knowledge that might allow treatments based on these factors to be timeoptimized. Methods: A randomized crossover experiment was designed to examine whether CIT shows morning/ evening variation in young, healthy adults (n ¼ 14, 5 women). On the first experimental day, subjects' shivering thresholds were determined following a cooling protocol. After z96 h had elapsed, the subjects then returned on two further days (approx. 48 h apart) at 08:00 h or 18:00 in random order. On both the latter days, the resting energy expenditure (REE) was measured before the subjects underwent personalized cold exposure (i.e., according to their shivering threshold). CIT was then assessed for 60 min by indirect calorimetry. In an independent cross-sectional study (n ¼ 133, 88 women), subjects came to the laboratory between 8:00 and 18:00 h and their BAT 18F-fluordeoxyglucose (18F-FDG) uptake was assessed after personalized cold stimulation. Results: Both the REE and CIT were similar in the morning and evening (all P > 0.05). Indeed, 60 min of personalized-mild cold exposure in the morning or evening elicited a similar change in energy expenditure (16.8 ± 12.8 vs. 15.7 ± 15.1% increase above REE, P ¼ 0.72). BAT 18F-FDG uptake was also similar in the morning, evening and afternoon (all P > 0.05). Conclusion: CIT does not appear to show morning/evening variation in young healthy adults, with the current study design and methodology. BAT 18F-FDG uptake appears not to change across the day either, although experiments with a within-subject study design are needed to confirm these findings., Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III PI13/01393 PTA 12264-I, Retos de la Sociedad DEP2016-79512-R, European Commission, Spanish Government FPU 13/03410 FPU 15/04059, Fundacion Iberoamericana de Nutricion (FINUT), Redes Tematicas de Investigaci on Cooperativa RETIC network Red SAMID RD16/0022, AstraZeneca, University of Granada's Plan Propio de Investigacion, Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR, Fundacion Alfonso Martin Escudero

Human brown adipose tissue (BAT) volume has been consistently claimed as inversely associated with whole-body adiposity. However, recent advances in the assessment of human BAT suggest that previously reported associations may have been biased. The present cross-sectional study investigates the association of BAT volume, mean radiodensity, and 18F-fluordeoxyglucose (18F-FDG) uptake (assessed via a static positron emission tomography-computerized tomography (PET-CT) scan after a 2-hour personalized cold exposure) with whole-body adiposity (measured by dual-energy X-ray absorptiometry) in 126 young adults (42 men/84 women; 25±5 kg/m2). BAT volume, but not 18F-FDG uptake, was positively associated with body mass index (BMI), fat mass, and visceral adipose tissue mass in men, but not in women. These associations were independent of the date when the PET-CT was performed, insulin sensitivity and body surface area. BAT mean radiodensity, an inverse proxy of BAT fat content, was negatively associated was with BMI, waist circumference, fat mass and visceral adipose tissue mas in men and with percentage fat mass in women. These results refute the widely held belief that human BAT volume is reduced in obese persons, at least in young adults, and suggest that it might even be the opposite in young men.

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.

Objective: To investigate the efficacy of three different 8h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) over 4 weeks on body weight and waist/hip circumferences in adults with overweight/obesity from southern Spain. Methods: A total of 22 adults with a baseline eating window ≥12h (13 women; 48 ± 10 years old; BMI: 32.7 ± 5.8 kg/m2) were randomly assigned to early (first meal within the first 2h after waking up), late (first meal 5-7h after waking up) or a self-selected (selecting the 8h eating window each day) TRE groups. Results: Body weight change was -1.7 ± 2.1kg (P=0.078), -0.8 ± 2.2kg (P=0.386), and -1.0 ± 0.9kg (P=0.020) for the early, late, and self-selected TRE groups. Changes in body weight and waist/hip circumferences did not differ across TRE groups (all P≥0.197; Figure 1). Conclusions: These results suggest that early, late, and self-selected TRE produce similar changes in body weight and waist/hip circumferences over 4 weeks in adults with overweight/obesity. Future, bigger, and longer studies are needed to confirm these findings. Figure 1. Changes in body weight and waist/hip circumferences across early (dark), late (gray), and self-selected (light) TRE groups. F statistic, P values and partial eta squared are from ANCOVAs adjusting for baseline values. M, males; F, females Disclosure M. Dote montero: None. J. R. Ruiz: None. R. Sevilla-lorente: None. E. Merchan-ramirez: None. J. Nunez-lopez: None. S. Mochon-benguigui: None. F. Amaro-gahete: None. F. Acosta: None. G. Sanchez-delgado: None. I. Labayen: None. Funding Spanish Ministry of Universities (FPU18/03357)

Human brown adipose tissue (BAT) volume has been consistently claimed as inversely associated with whole-body adiposity. However, recent advances in the assessment of human BAT suggest that previously reported associations may have been biased. The present cross-sectional study investigates the association of BAT volume, mean radiodensity, and 18F-fluordeoxyglucose (18F-FDG) uptake (assessed via a static positron emission tomography-computerized tomography (PET-CT) scan after a 2-hour personalized cold exposure) with whole-body adiposity (measured by dual-energy X-ray absorptiometry) in 126 young adults (42 men / 84 women; 25±5 kg/m2). BAT volume, but not 18F-FDG uptake, was positively associated with body mass index (BMI), fat mass, and visceral adipose tissue mass in men, but not in women. These associations were independent of the date when the PET-CT was performed, insulin sensitivity and body surface area. BAT mean radiodensity, an inverse proxy of BAT fat content, was negatively associated was with BMI, waist circumference, fat mass and visceral adipose tissue mas in men and with percentage fat mass in women. These results refute the widely held belief that human BAT volume is reduced in obese persons, at least in young adults, and suggest that it might even be the opposite in young men.

Objective: To study the association between usual dietary factors (dietary energy density, nutrient intake, food group consumption, and dietary pattern) and brown adipose tissue (BAT) volume/F-18-fluorodeoxyglucose (F-18-FDG) uptake after personalized cold exposure in young healthy adults.Methods: A total of 122 young adults (n = 82 women; 22.0 +/- 2.1 years old; 24.8 +/- 4.8 kg/m(2)) took part in this cross-sectional study. Dietary factors were measured via a food frequency questionnaire and three non-consecutive 24 h recalls. Dietary energy density (foods and caloric beverages included) and macronutrient intakes were subsequently estimated using EvaIFINUT (R) software, food group consumption was estimated from the food frequency questionnaire, and different dietary patterns and quality indices were determined according to the reference methods. BAT volume, BAT F-18-FDG uptake, and skeletal muscle F-18-FDG uptake were assessed by static F-18-FDG positron-emission tomography and computed tomography (PET-CT) scans after a 2 h personalized exposure to cold.Results: A direct association was detected between dietary energy density and BAT Standardized Uptake Value (SUV)mean (beta = 0.215; R-2 = 0.044; P = 0.022), and between ethanol consumption and BAT volume (beta = 0.215; R-2 = 0.044; P = 0.022). The a priori Mediterranean dietary pattern was inversely associated with BAT SUVmean and SUVpeak (beta = -0.273; R-2 = 0.075; P = 0.003 and beta = -0.255; R-2 = 0.066; P = 0.005 respectively). In addition, the diet quality index for a Mediterranean diet and a pro-inflammatory dietary pattern (as determined via the dietary inflammatory index) were directly associated with BAT SUVmean and SUVpeak (SUVmean: beta = 0.238; R-2 = 0.053; P = 0.013 and beta = 0.256; R-2 = 0.052; P = 0.012 respectively; SUVpeak: beta = 0.278; R-2 = 0.073; P = 0.003 and beta = 0.248; R-2 = 0.049; P = 0.016 respectively). After controlling for multiplicity and possible confounders (sex, the evaluation wave and BMI), all the detected associations persisted.Conclusion: Dietary factors are slightly associated with BAT volume and/or F-18-FDG uptake after a personalized cold exposure in young adults. Our results provide an overall picture of the potential relationships between dietary factors and BAT-related variables in humans. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

To summarize the state-of-the-art regarding the exercise-regulated endocrine signals that might modulate brown adipose tissue (BAT) activity and/or white adipose tissue (WAT) browning, or through which BAT communicates with other tissues, in humans. Exercise induces WAT browning in rodents by means of a variety of physiological mechanism. However, whether exercise induces WAT browning in humans is still unknown. Nonetheless, a number of protein hormones and metabolites, whose signaling can influence thermogenic adipocyte’s metabolism, are secreted during and/or after exercise in humans from a variety of tissues and organs, such as the skeletal muscle, the adipose tissue, the liver, the adrenal glands, or the cardiac muscle. Overall, it seems plausible to hypothesize that, in humans, exercise secretes an endocrine cocktail that is likely to induce WAT browning, as it does in rodents. However, even if exercise elicits a pro-browning endocrine response, this might result in a negligible effect if blood flow is restricted in thermogenic adipocyte–rich areas during exercise, which is still to be determined. Future studies are needed to fully characterize the exercise-induced secretion (i.e., to determine the effect of the different exercise frequency, intensity, type, time, and volume) of endocrine signaling molecules that might modulate BAT activity and/or WAT browning or through which BAT communicates with other tissues, during exercise. The exercise effect on BAT metabolism and/or WAT browning could be one of the still unknown mechanisms by which exercise exerts beneficial health effects, and it might be pharmacologically mimicked.

To study the association between usual dietary factors (dietary energy density, nutrient intake, food group consumption, and dietary pattern) and brown adipose tissue (BAT) volume/A total of 122 young adults (n = 82 women; 22.0 ± 2.1 years old; 24.8 ± 4.8 kg/mA direct association was detected between dietary energy density and BAT Standardized Uptake Value (SUV)mean (β = 0.215; RDietary factors are slightly associated with BAT volume and/or

Undercarboxylated osteocalcin (ucOC) could be a biomarker of glucose disturbances and cardiovascular risk. Our study aimed to determine the association between serum levels of ucOC and cardiovascular risk in metabolic syndrome (MetS) patients and to analyse its potential role as estimator of type 2 diabetes (T2D) risk in this population. This cross-sectional study included 235 patients with MetS, 53.2% women, aged 55–75 years. Circulating ucOC levels were measured by ELISA. Cardiovascular risk was determined as Z-score of the diagnostic criteria for MetS (CV-ZS). Linear regression model was performed to analyse the association between circulating ucOC and CV-ZS. A receiver operating curve (ROC) was performed to analyse the usefulness of ucOC as T2D risk estimator. Patients above the CV-ZS median showed signifcant lower ucOC levels. We found an inverse association between ucOC levels and CV-ZS in MetS patients without T2D. Patients with ucOC levels below the 25th percentile showed worse cardiometabolic profle and higher cardiovascular and T2D risk. The area under the curve performed better when ucOC levels were included along with the classic T2D risk factors. The measurement of circulating ucOC could be a useful tool to identify increased cardiovascular and T2D risk in MetS patients without T2D., Junta de Andalucia PI-0207-2016, European Union (EU) PI18-00803 PI18-01235

Heart rate variability (HRV) is a non-invasive indicator of autonomic nervous system function. HRV recordings show artefacts due to technical and/or biological issues. The Kubios software is one of the most used software to process HRV recordings, offering different levels of threshold-based artefact correction (i.e., Kubios filters). The aim of the study was to analyze the impact of different Kubios filters on the quantification of HRV derived parameters from short-term recordings in three independent human cohorts. A total of 312 participants were included: 107 children with overweight/obesity (10.0 &plusmn, 1.1 years, 58% men), 132 young adults (22.2 &plusmn, 2.2 years, 33% men) and 73 middle-aged adults (53.6 &plusmn, 5.2 years, 48% men). HRV was assessed using a heart rate monitor during 10&ndash, 15 min, and the Kubios software was used for HRV data processing using all the Kubios filters available (i.e., 6). Repeated-measures analysis of variance indicated significant differences in HRV derived parameters in the time-domain (all p &lt, 0.001) across the Kubios filters in all cohorts, moreover similar results were observed in the frequency-domain. When comparing two extreme Kubios filters, these statistical differences could be clinically relevant, e.g. more than 10 ms in the standard deviation of all normal R-R intervals (SDNN). In conclusion, the results of the present study suggest that the application of different Kubios filters had a significant impact on HRV derived parameters obtained from short-term recordings in both time and frequency-domains.

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.

Regular physical activity (PA) is an important part of the treatment of several medical conditions, including overweight and obesity, in which there may be a weakened appetite control. Eating behaviour traits influence weight control and may be different in active and sedentary subjects. This paper reports the relationships between the time spent in sedentary behaviour and physical activity (PA) of different intensity, and eating behaviour traits in young, healthy adults. Additionally, it reports the results of a six-month-long, randomized, controlled trial to examine the effect of an exercise intervention on eating behaviour traits. A total of 139 young (22.06 &plusmn, 2.26 years) healthy adults (68.35% women) with a Body Mass Index (BMI) of 24.95 &plusmn, 4.57 kg/m2 were enrolled. Baseline assessments of habitual PA were made using wrist-worn triaxial accelerometers, eating behaviour traits were examined via the self-reported questionnaires: Binge Eating, Three-Factor Eating Questionnaire-R18 and Control of Eating Questionnaire. The subjects were then randomly assigned to one of three groups: control (usual lifestyle), moderate-intensity exercise (aerobic and resistance training 3&uml, C4 days/week at a heart rate equivalent to 60% of the heart rate reserve (HRres) for the aerobic component, and at 50% of the 1 repetition maximum (RM) for the resistance component), or vigorous-intensity exercise (the same training but at 80% HRres for half of the aerobic training, and 70% RM for the resistance training). At baseline, sedentary behaviour was inversely associated with binge eating (r = &minus, 0.181, p &lt, 0.05) and with uncontrolled eating (r = &minus, 0.286, p = 0.001). Moderate PA (MPA) was inversely associated with craving control (r = &minus, 0.188, p &lt, 0.05). Moderate-to-vigorous PA (MVPA) was directly associated with binge eating (r = 0.302, p &lt, 0.001) and uncontrolled eating (r = 0.346, p &lt, 0.001), and inversely associated with craving control (r = &minus, 0.170, p &lt, 0.015). Overall, PA was directly associated with binge eating (r = 0.275, p = 0.001), uncontrolled eating (r = 0.321, p &lt, 0.001) and emotional eating (r = 0.204, p &lt, 0.05). Additionally, only emotional eating was modified by the intervention, increasing in the vigorous-intensity exercise group (p &lt, 0.05). In summary, we observed that time spent in sedentary behaviour/PA of different intensity is associated with eating behaviour traits, especially binge eating in young adults. In contrast, the six-month exercise intervention did not lead to appreciable changes in eating behaviour traits.

Procedures: We measured 125 individuals after a personalized cooling protocol with a static [18F]FDG-PET/CT scan. We quantified BAT using different combination of threshold in every single HU for all participants. Results: We observed that the SUV threshold influences BAT quantification by [18F]FDG-PET/ CT scans more than the HU range. We found that the range from − 50 to − 10 HU had the highest proportion of total BAT volume (43.2 %), which represents 41.4 % of the total BAT metabolic activity in our cohort. We also observed that BAT volume was not different between categories of body mass index, as well as BAT activity (SUVmean). In addition, BAT was less dense in women than in men, although the BAT activity (SUVmean) was higher in all ranges of HU. We also observed that the radiodensity of BAT located in the cervical area was mainly in the range from − 50 to − 10 HU. Conclusion: Therefore, all future human studies using static [18F]FDG-PET/CT scans should include BAT in the radiodensity range from − 50 to − 10 HU., This study was supported by the Spanish Ministry of Economy and Competitiveness, Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393) and Retos de la Sociedad (DEP2016-79512-R), Fondos Estructurales de la Unión Europea (FEDER), by the Spanish Ministry of Education (FPU 13/04365), by the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016 - Excellence actions: Unit of Excellence on Exercise and Health (UCEES) - and Plan Propio de Investigación 2018 - Programa Contratos-Puente, and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (FEDER, ref. SOMM17/6107/UGR).

New findings What is the central question of this study? In some studies, biopsies have been performed of the subcutaneous adipose tissue in the abdomen, and they failed to find browning markers. Is the abdomen the right place to take biopsies? What is the main finding and its importance? For first time, we observed that the glucose uptake in the dorsocervical subcutaneous adipose tissue is higher in comparison to other areas of subcutaneous adipose tissue. Abstract Neonates have subcutaneous brown adipose tissue (BAT) in the dorsocervical area, and it is thought that these depots gradually disappear with age. Here, we determined that young adults have high 18 F-flurodeoxyglucose (18 F-FDG) uptake in the subcutaneous adipose tissue (SAT) of the dorsocervical area. A total of 133 young adults (age 22 ± 2 years; body mass index 25 ± 5 kg m2 ) were included in the study. We performed a shivering threshold test for every participant. Later, we performed 2 h of personalized cold exposure, immediately before a positron emission tomography/computed tomography scan. We showed that 23 of 133 participants had 18 F-FDG uptake in the dorsocervical area that achieved the criteria to be considered BAT, mainly in women (96%, n = 22 of 23). In the whole sample, the glucose uptake in the SAT of the dorsocervical area was positively correlated with BAT volume and activity located in the supraclavicular area. We showed that the 18 F-FDG uptake of the SAT of the dorsocervical area in humans is different from that of other SAT areas. Future studies are warranted to confirm the brown signature of this tissue.

Brown adipose tissue (BAT) activity is influenced by the outdoor temperature variation. However, people spend most of their time indoors, especially in colder regions and during cold seasons. Therefore, outdoor temperature is probably not an accurate tool to quantify the exposure of the participants before BAT quantification. We studied the association of wrist and personal environmental temperatures with cold-induced BAT and skeletal muscle [18F]fluorodeoxyglucose ([18F]FDG) uptake in adults. A total of 74 participants wore two iButtons during 7 days to measure wrist temperature (WT) and personal level of environmental temperature (Personal-ET). Thereafter, we performed a 2-h personalized cooling protocol before performing an [18F]FDG-PET/CT scan. WT was negatively associated with BAT volume ( R2 = 0.122; P = 0.002) and BAT activity [standardized uptake value (SUV)peak, R2 = 0.083; P = 0.012]. Moreover, Personal-ET was negatively associated with BAT volume ( R2 = 0.164; P < 0.001), BAT activity (SUVmean and SUVpeak, all R2 ≥ 0.167; P < 0.001), and skeletal muscle activity (SUVpeak, R2 = 0.122; P = 0.002). Interestingly, the time exposed to a certain Personal-ET (16–20°C) positively correlated only with [18F]FDG uptake by BAT (volume and activity; all P ≤ 0.05), whereas the time exposed to 12–15°C positively correlated only with measures of [18F]FDG uptake by skeletal muscle activity (all P ≤ 0.05). This study shows that WT and Personal-ET are associated with [18F]FDG uptake by BAT and skeletal muscle activity in adults within certain temperature thresholds. Moreover, our results suggest that [18F]FDG uptake by human BAT or skeletal muscle can be activated or inhibited in different ranges of ambient temperatures exposures. Results should be taken with caution because the observed associations were relatively weak.

(1) To examine the comparability, i.e., discriminatory power, in a preschooler test (PREFIT 20-m shuttle-run test) and the 20mSRT-Original in 5–6-year-olds; (2) to provide an equation to estimate VO2max from the 20mSRT-PREFIT. 138 participants aged 5–6 years performed the 20mSRT-PREFIT and the 20mSRT-Original in a counterbalanced order. Total test duration, completed stages, maximum speed and maximum heart rate were registered. Participants finished stages from 2–10 in the 20mSRT-PREFIT, whereas stages 1–5 were completed in the 20mSRT-Original and a null was registered, showing the original version a lower discriminatory power. We also observed that the higher the cardiorespiratory fitness level the more comparable were the tests, i.e., − 0.04 km h−1 difference between tests in the fittest participants (i.e., maximum speed ≥ 9.5 km h−1). Using the original equation proposed by Leger and colleagues in 1988 and based on the estimation regression of maximum speed in the 20mSRT-Original from the PREFIT version, we computed a new equation to estimate VO2max from the 20mSRT-PREFIT: Y = 44.657 + 1.795X 1 − 2.601X 2 + 0.0852X 1 X 2 (r = 0.77; r 2 = 0.59; SEE = 1.25 ml kg−1 min−1 or 2.59% of estimated mean VO2max = 48.38 ml kg−1 min−1), where X 1 is the 20mSRT-PREFIT maximum speed (km h−1) and X 2 is the age of participants. The 20mSRT-PREFIT resulted in a significantly higher maximum heart rate than the 20mSRT-Original. The 20mSRT-PREFIT has higher discriminatory power than the 20mSRT-Original. Our study provides for the first time an opportunity to estimate VO2max in preschoolers and children based on the 20mSRT-PREFIT maximum speed and the age of participants.

Study Objectives Short sleep duration and sleep disturbances have been related to obesity and metabolic disruption. However, the behavioral and physiological mechanisms linking sleep and alterations in energy balance and metabolism are incompletely understood. In rodents, sleep regulation is closely related to appropriate brown adipose tissue (BAT) thermogenic activity, but whether the same is true in humans has remained unknown. The present work examines whether sleep duration and quality are related to BAT volume and activity (measured by 18F-FDG) and BAT radiodensity in humans. Methods A total of 118 healthy adults (69% women, 21.9 ± 2.2 years, body mass index: 24.9 ± 4.7 kg/m2) participated in this cross-sectional study. Sleep duration and other sleep variables were measured using a wrist-worn accelerometer for seven consecutive days for 24 hours per day. The Pittsburgh Sleep Quality Index was used to assess sleep quality. All participants then underwent a personalized cold exposure to determine their BAT volume, activity, and radiodensity (a proxy of the intracellular triglyceride content), using static positron emission tomography combined with computed tomography (PET/CI) scan. Results Neither sleep duration nor quality was associated with BAT volume or activity (the latter represented by the mean and peak standardized 18F-FDG uptake values) or radiodensity (all p > .1). The lack of association remained after adjusting the analyses for sex, date of PET/CT, and body composition. Conclusions Although experiments in rodent models indicate a strong relationship to exist between sleep regulation and BAT function, it seems that sleep duration and quality may not be directly related to the BAT variables examined in the present work. Clinical Trial Registration NCT02365129 (ClinicalTrials.gov).

Background & aims: Since the discovery of active brown adipose tissue in human adults, non-shivering cold-induced thermogenesis (CIT) has been regarded as a promising tool to combat obesity. However, there is a lack of consensus regarding the method of choice to analyze indirect calorimetry data from a CIT study. We analyzed the impact of methods for data selection and methods for data analysis on measures of cold-induced energy expenditure (EE) and nutrient oxidation rates.Methods: Forty-four young healthy adults (22.1 +/- 2.1 years old, 25.6 +/- 5.2 kg/m(2), 29 women) participated in the study. Resting metabolic rate (RMR), cold-induced thermogenesis (CIT), and cold-induced nutrient oxidation rates were estimated by indirect calorimetry under fasting conditions during 1 h of cold exposure combining air conditioning (19.5-20 degrees C) and a water perfused cooling vest set at a temperature of 4 degrees C above the individual shivering threshold. We applied three methods for data selection: (i) time intervals every 5 min (5min-TI), (ii) the most stable 5-min period of every forth part of the cold exposure (5min-SS-4P), and (iii) the most stable 5-min period of every half part of the cold exposure (5min-SS-2P). Lately we applied two methods for data analysis: (i) area under the curve as a percentage of the baseline RMR (AUC) and; (ii) the difference between EE at the end of the cold exposure and baseline RMR (Last-RMR).Results: Mean overall CIT estimation ranged from 11.6 +/- 10.0 to 20.1 +/- 17.2 %RMR depending on the methods for data selection and analysis used. Regarding methods for data selection, 5min-SS-2P did not allow to observe physiologically relevant phenomena (e.g. metabolic shift in fuel oxidation; P = 0.547) due to a lack of resolution. The 5min-TI and 5min-SS-4P methods for data selection seemed to be accurate enough to observe physiologically relevant phenomena (all P < 0.014), but not comparable for estimating over-all CIT and cold-induced nutrient oxidation rates (P < 0.01). Regarding methods for data analysis, the AUC seemed to be less affected for data artefacts and to be more representative in participants with a non-stable energy expenditure during cold exposure.Conclusions: The methods for data selection and analysis can have a profound impact on CIT and cold-induced nutrient oxidation rates estimations, and therefore, it is mandatory to unify it across scientific community to allow inter-study comparisons. Based on our findings, 5min-TI should be considered the method of choice to study dynamics (i.e. changes across time) of CIT and cold-induced nutrient oxidation rates, while 5min-SS-4P and AUC should be the method of choice when computing CIT and cold-induced nutrient oxidation rates as a single value. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

This study compares the influence of different exercise training programs on basal metabolic rate (BMR) and fat oxidation, in basal conditions (BFox) and during exercise (MFO), in sedentary, middle-aged adults.The study subjects of this 12 week-long, randomised controlled trial, were 71 middle-aged adults (age 53.5 ± 4.9 years; 52% women). Subjects were randomly assigned to one of the following groups: (1) no exercise, (2) concurrent training based on international physical activity recommendations (PAR group), (3) high intensity interval training (HIIT group), and (4) high intensity interval training plus whole-body electromyostimulation (HIIT + EMS group). Subject BMR, BFox and MFO were determined by indirect calorimetry before and after the intervention.The HIIT + EMS subjects showed significant increases in BFox following the intervention compared with the control group (all P = 0.043); no such differences were seen in the PAR and HIIT compared with the control group (all P ≥ 0.1). A significant increase in post-intervention MFO was noted for the HIIT and HIIT + EMS group compared to the non-exercise control group (P 0.05); no such difference was seen in the PAR group compared to the control group (all P ≥ 0.05).Twelve weeks of high intensity interval training plus whole-body electromyostimulation may increase the BFox and MFO of middle-aged sedentary adults. These findings have important clinical implications; a well-designed high-intensity interval training program plus whole-body electromyostimulation might be followed to help combat the appearance of chronic metabolic diseases characterized by metabolic inflexibility in middle-aged sedentary adults, though it will be necessary to determine how long the effects last.