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A primary function of HIV-1 Nef is the enhancement of viral infectivity and replication. Whether counteraction of the antiretroviral proteins SERINC3 and SERINC5 is the cause of this positive influence on viral growth-rate and infectivity remains unclear. Here, we utilized CRISPR/Cas9 to knockout SERINC3 and SERINC5 in a leukemic CD4-positive T cell line (CEM) that displays nef-related infectivity and growth-rate phenotypes. Viral replication was attenuated in CEM cells infected with HIV-1 lacking Nef (HIV-1ΔNef). This attenuated growth-rate phenotype was observed regardless of whether the coding regions of the serinc3 or serinc5 genes were intact. Moreover, knockout of serinc5 alone or of both serinc5 and serinc3 together failed to restore the infectivity of HIV1ΔNef virions produced from infected CEM cells. Our results corroborate a similar study using another T-lymphoid cell line (MOLT-3) and indicate that the antagonism of SERINC3 and SERINC5 does not fully explain the virology of HIV-1 lacking Nef.

Despite many decades of research examining thermoregulatory responses under varying cold stresses in humans, very little is known about the variability in metabolic heat production and shivering activity. Here, we used a novel closed-loop mean skin temperature clamping technique with a liquid-conditioned suit to isolate the effects of mean skin temperature on the subjective evaluation of thermal sensation, heat production, shivering responses, and oxidative fuel selection in young, lean, and healthy men ( n = 12) and women ( n = 12). Our results showed a skin temperature-dependent increase in metabolic heat production (5.2 ± 1.2 kJ/min, 5.9 ± 1.5 kJ/min, and 7.0 ± 1.8 kJ/min with skin temperature maintained at 31 ± 0.1°C, 29 ± 0.2°C, and 27 ± 0.1°C, respectively; P < 0.0001) and shivering intensity in both men and women [0.6 ± 0.1% maximal voluntary contraction (MVC), 1.1 ± 0.4% MVC, and 2.5 ± 0.7% MVC, respectively; P < 0.0001], including sex-dependent differences in heat production at all three temperatures ( P < 0.005). Even when controlling for lean body mass and fat mass, sex differences persisted ( P = 0.048 and P = 0.004, respectively), whereas controlling for differences in body surface area eliminated these differences. Interestingly, there were no sex differences in the cold-induced change in thermogenesis. Despite clamping skin temperature, there was tremendous variability in the rate of heat production and shivering intensity. Collectively this data suggests that many of the interindividual differences in thermogenesis and shivering may be explained by differences in morphology and body composition.

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: 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 role of lifestyle behaviors on neck adipose tissue (NAT), a fat depot that appears to be involved in the pathogenesis of different cardiometabolic diseases and in inflammatory status, is unknown. In this cross-sectional and exploratory study, the authors examined the relationship between sedentary time and physical activity (PA) with neck adiposity in young adults. A total of 134 subjects (69% women, 23 ± 2 years) were enrolled. The time spent in sedentary behavior and PA of different intensity were objectively measured for 7 consecutive days (24 hr/day), using a wrist (nondominant)-worn accelerometer. The NAT volume was assessed using computed tomography, and the compartmental (subcutaneous, intermuscular, and perivertebral) and total NAT volumes were determined at the level of vertebra C5. Anthropometric indicators and body composition (by dual-energy X-ray absorptiometry) were determined. The time spent in light physical activity and moderate physical activity (MPA) and the overall PA were inversely associated with the intermuscular NAT volume in men, as were the MPA and overall PA with total NAT volume (all ps ≤ .04). Sedentary time was directly related to the total NAT volume (p = .04). An opposite trend was observed in women, finding a direct relationship of MPA with the subcutaneous NAT; of light physical activity, MPA, and overall PA with the perivertebral NAT; and of light physical activity with total NAT volumes (all ps ≤ .05). The observed associations were weak, and after adjusting for multiplicity, the results became nonsignificant (p > .05). These findings suggest that the specific characteristics of PA (time and intensity) might have sex-dependent implications in the accumulation of NAT.

This study aimed to examine the association of heart rate (HR) and heart rate variability (HRV) with cardiorespiratory fitness (CRF) in adults. This cross-sectional study included 204 participants: 132 young adults (67% women; 22.3 ± 2.3 years) and 72 middle-aged adults (53% women; 53.2 ± 5 years). HR and HRV were measured using a Polar RS800CX heart rate monitor. CRF was assessed using a metabolic cart during an incremental test. HR was negatively associated with CRF relative to body weight (BW) in young adults adjusting for sex, age, and physical activity (β ranged from -0.200 to -0.195; all

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.

The study was supported by the Spanish Ministry of Economy and Competitiveness via Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393) and PTA 12264-I, Retos de la Sociedad (DEP2016-79512-R), and European Regional Development Funds (ERDF), by the Spanish Ministry of Education (FPU16/05159, FPU16/02828 and FPU17/01523), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas De Investigacion Cooperativa RETIC (Red SAMID RD16/0022), the Chinese Scholarship Council (CSC, No. 201707060012 to XD), InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530), Fundacion Alfonso Martin Escudero and Maria Zambrano fellowship by the Ministerio de Universidades y la Union Europea-NextGenerationEU (RR_C_2021_04). AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucia, Consejeria de Economia, Conocimiento, Empresas y Universidad (ref. P18-RT-4455). AL and RVV are supported by the funds of European Commission through the "European funds for regional development" (EFRE) as well as by the regional Ministry of Economy, Science and Digitalization of Saxony-Anhalt as part of the "Autonomy in old Age" (AiA) research group for "LiLife" Project (Project ID: ZS/2018/11/95324). M.C-P was recipient of a postdoctoral grant (DOC_00448) from the Consejeria de Economia, Industria, Conocimiento Universidades (PAIDI 2020, Junta de Andalucia), Spain, cofunded by the Fondo Europeo de Desarrollo Regional (FEDER). We would like to thank the team of Data Integration Center of University Medicine Magdeburg for local data-analysis solutions; they are supported by MIRACUM and funded by the German Federal Ministry of Education and Research (BMBF) within the "Medical Informatics Funding Scheme" (FKZ 01ZZ1801H)., Objective: To investigate the association of plasma levels of endocannabinoids with fecal microbiota. Methods: Plasma levels of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as well as their eleven analogues, and arachidonic acid (AA), were measured using liquid chromatography-tandem mass spectrometry in 92 young adults. DNA extracted from stool samples was analyzed using 16S rRNA gene sequencing. Lipopolysaccharide levels were measured in plasma samples. Results: Plasma levels of endocannabinoids and their analogues were not related to beta or alpha diversity indexes. Plasma levels of AEA and related N-acylethanolamines correlated positively with the relative abundance of Faecalibacterium genus (all rho >= 0.26, p = 0.22, p = 0.24, p = 0.27, p, Spanish Ministry of Economy and Competitiveness via Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III PI13/01393 PTA 12264-I DEP2016-79512-R, European Commission Spanish Government FPU16/05159 FPU16/02828 FPU17/01523, Fundacion Iberoamericana de Nutricion (FINUT), Redes Tematicas De Investigacion Cooperativa RETIC Red SAMID RD16/0022, China Scholarship Council 201707060012, InFLAMES Flagship Programme of the Academy of Finland 337530, Ministerio de Universidades y la Union Europea-NextGenerationEU RR_C_2021_04, AstraZeneca, University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Junta de Andalucia P18-RT-4455, European Commission through the "European funds for regional development" (EFRE), regional Ministry of Economy, Science and Digitalization of Saxony-Anhalt as part of the "Autonomy in old Age" (AiA) research group for "LiLife" Project ZS/2018/11/95324, Consejeria de Economia, Industria, Conocimiento Universidades (PAIDI 2020, Junta de Andalucia), Spain DOC_00448, European Commission, Spanish Government, MIRACUM, Federal Ministry of Education & Research (BMBF) FKZ 01ZZ1801H

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

Objectives Neck adipose tissue (NAT) volume increases with general adiposity, with fat accumulating in different neck tissue compartments. In patients with certain malignant/benign tumours, the accumulation of NAT, and certain NAT distributions, have been associated with cardiometabolic risk (CMR). However, it is unknown whether the same relationships exist in healthy people, and whether NAT accumulation and distribution are related to the inflammatory status. Methods In this cross-sectional study, 139 young healthy adults (68% women) underwent a computed tomography scan to quantify the volume of compartmental (i.e., subcutaneous, intermuscular and perivertebral) and total NAT at the height of vertebra C5. Anthropometric indicators were measured, and body composition determined using dual energy X-ray absorptiometry. Information on CMR factors (i.e., blood glycaemic and lipid markers, blood pressure and physical fitness) was also gathered, and a CMR score calculated. Several plasma cytokines and serum components of the innate immune system were measured to determine the inflammatory status. Results Compartmental and total NAT volumes were directly related to body mass index (BMI), and lean, fat, and visceral adipose tissue (VAT) masses (all, P

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.

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.

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

Physical fitness (PF) is a cornerstone of metabolic health. However, its role in maternal–fetal metabolism during pregnancy is poorly understood. The present work investigates: (i) the association of PF with maternal and fetal cardiometabolic markers, and with clustered cardiometabolic risk during pregnancy, and (ii) whether being fit counteracts cardiometabolic abnormalities associated with overweight/obesity. Several PF components (flexibility, lower and upper body strength, and cardiorespiratory fitness [CRF]) were objectively assessed in 151 pregnant women at gestational weeks 16 and 33, and an overall PF cluster score calculated. At the same times, maternal glycemic and lipid markers, cortisol, and C-reactive protein were assessed with standard biochemical methods, along with blood pressure and a proxy for insulin resistance, and a cardiometabolic risk cluster score determined. These analytes were also measured in maternal and umbilical cord arterial and venous blood collected at delivery. PF was found to be associated with several maternal and a small number of fetal cardiometabolic markers (p p p

This study examines (a) the influence of exercise, lifestyle behavior components (sedentary time, physical activity, and sleep and dietary patterns), and physical fitness on maternal weight gain, postpartum weight retention, and excessive gestational weight gain and (b) whether exercise protects against the adverse effects of impaired metabolism and nonoptimal body composition related to excessive gestational weight gain. Subjects were assigned to either a supervised concurrent (aerobic + resistance) exercise program followed 3 days/week (n = 47) or a control group (n = 54). Sedentary time, physical activity, sleep and dietary patterns (assessed by accelerometry and questionnaires), muscle strength (handgrip test), and cardiorespiratory fitness (Bruce test) were determined at gestational Weeks 16 and 33 (early-middle and late pregnancy, respectively), and at 6 weeks postpartum. Weight gain and weight retention were calculated using recorded weights at prepregnancy, early-middle, and late pregnancy, and at 6 weeks postpartum. Birth complications, maternal postpartum body composition, cardiometabolic, and inflammatory markers in maternal and umbilical cord arterial and venous blood, and in colostrum, and mature milk were also recorded. The exercise intervention reduced late weight gain (B = −2.7, SE = 0.83, p = .003) and weight retention (B = −2.85, SE = 1.3, p = .03), independent of any lifestyle behavior component or physical fitness, but did not prevent excessive weight gain. Increasing cardiorespiratory fitness, muscle strength, and sleep duration were associated with a smaller mean weight gain and lower excessive weight gain values (p p

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 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)

Thanks to Dr. Herman Pontzer (Duke University) for his valuable feedback. We also thank the following agencies for their funding: Fondo Nacional de Desarrollo Científico y Tecnológico (11180361 to R.F.-V.); Spanish Ministry of Education, Culture and Sport (FPU15/04059 to J.M.A.A.; FPU15/02645 to J.H.M.; FPU14/04172 to F.J.A.-G.); University of Granada (Plan Propio de Investigación 2019 [Programa Contratos-Puente] to F.J.A.-G.; Plan Propio de Investigación 2016 [Excellence actions: Unit of Excellence on Exercise and Health UCEES]); Spanish Ministry of Economy and Competitiveness (ACTIBATE study; ACTIVEBRAINS study); Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393 to ACTIBATE study); Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Funds (FEDER: ref. SOMM17/6107/UGR to ACTIBATE study); Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022 to ACTIBATE study); EXERNET Research Network on Exercise and Health in Special Populations (DEP2005-00046/ACTI); Fundación Iberoamericana de Nutrición (ACTIBATE study); AstraZeneca HealthCare Foundation (ACTIBATE study); PTA 12264-I to FIT-AGEING study., Supplementary Information The online version contains supplementary material available at https://doi. org/10.1038/s41598-021-91750-x., The constrained total energy expenditure (TEE) model posits that progressive increases in physical activity (PA) lead to increases in TEE; but after certain PA threshold, TEE plateaus. Then, a compensatory reduction in the expenditure of non-essential activities constrains the TEE. We hypothesized that high PA levels as locomotion associate with a compensatory attenuation in arm movements. We included 209 adults (64% females, mean [SD] age 32.1 [15.0] years) and 105 children (40% females, age 10.0 [1.1] years). Subjects wore, simultaneously, one accelerometer in the non-dominant wrist and another in the hip for ≥ 4 days. We analyzed the association between wrist-measured (arm movements plus locomotion) and hip-measured PA (locomotion). We also analyzed how the capacity to dissociate arm movements from locomotion influences total PA. In adults, the association between wrist-measured and hip-measured PA was better described by a quadratic than a linear model (Quadratic-R2 = 0.54 vs. Linear-R2 = 0.52; P = 0.003). Above the 80th percentile of hip-measured PA, wrist-measured PA plateaued. In children, there was no evidence that a quadratic model fitted the association between wrist-measured and hip-measured PA better than a linear model (R2 = 0.58 in both models, P = 0.25). In adults and children, those with the highest capacity to dissociate arm movements from locomotion—i.e. higher arm movements for a given locomotion—reached the highest total PA. We conclude that, in adults, elevated locomotion associates with a compensatory reduction in arm movements (probably non-essential fidgeting) that partially explains the constrained TEE model. Subjects with the lowest arm compensation reach the highest total PA., AstraZeneca HealthCare Foundation PTA 12264-I, EXERNET Research Network on Exercise and Health in Special Populations DEP2005-00046/ACTI, Fundación Iberoamericana de Nutrición, Fondo Nacional de Desarrollo Científico y Tecnológico 11180361 FONDECYT, Ministerio de Economía y Competitividad MINECO, Instituto de Salud Carlos III PI13/01393 ISCIII, Universidad de Granada UGR, European Regional Development Fund RD16/0022,SOMM17/6107/UGR ERDF, Consejería de Conocimiento, Investigación y Universidad, Junta de Andalucía, Vicerrectorado de Investigación y Transferencia, Universidad de Granada Health [UCEES]),Plan Propio de Investigación 2016 (Excellence actions: Unit of Excellence on Exercise,Plan Propio de Investigación 2019 (Programa Contratos-Puente)

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.

The 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 CB16/10/00239) and PTA 12264-I, Retos de la Sociedad (DEP2016-79512-R), and European Regional Development Funds (ERDF). Other funders included the Spanish Ministry of Education (FPU 16/05159, 15/04059 and 19/02326), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas De Investigacion Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca Health Care Foundation, the University of Granada Plan Propio de Investigacion 2016 (Excellence actions: Unit of Excellence on Exercise, Nutrition and Health [UCEENS]), and by the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF, SOMM17/6107/UGR). AMT was supported by Seneca Foundation through grant 19899/GERM/15 and the Ministry of Science Innovation and Universities RTI2018-093528-B-I0, as well as DJP (MINECO; RYC-2014-16938). BMT was supported by an individual postdoctoral grant from the Fundacion Alfonso Martin Escudero. We thank Dr. Matt Smith of Embr Labs Inc. for configuring the Embr Wave (R) devices used in this experiment., Where people live and work together it is not always possible to modify the ambient temperature; ways must therefore be found that allow individuals to feel thermally comfortable in such settings. The Embr Wave (R) is a wrist-worn device marketed as a 'personal thermostat' that can apply a local cooling stimulus to the skin. The aim of the present study was to determine the effect of an intermittent mild cold stimulus of 25 degrees C for 15-20 s every 5 min over 3.5 days under free-living conditions on 1) skin temperature, 2) perception of skin temperature, 3) sleep quality and 4) resting energy expenditure (REE) in young, healthy adults. Ten subjects wore the device for 3.5 consecutive days. This intervention reduced distal skin temperature after correcting for personal ambient temperature (P < 0.05), but did not affect the subjects' the perception of skin temperature, sleep quality or REE (all P >= 0.051). Thus, this intermittent mild cold regime can reduce distal skin temperature, and wearing it under free-living conditions for 3.5 days does not seem to impair the perception of skin temperature and sleep quality or modify REE., Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III PI13/01393 CB16/10/00239, PTA 12264-I, Retos de la Sociedad DEP2016-79512-R, European Commission, Spanish Government 16/05159 15/04059 19/02326, Fundacion Iberoamericana de Nutricion (FINUT), Redes Tematicas De Investigacion Cooperativa RETIC (Red SAMID) RD16/0022, AstraZeneca, University of Granada Plan Propio de Investigacion, Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR, Fundacion Seneca 19899/GERM/15, Ministry of Science Innovation and Universities RTI2018-093528-B-I0, MINECO RYC-2014-16938, Fundacion Alfonso Martin Escudero

A.P.-F. and J.M.A.: conception and design, statistical analysis, interpretation of data, writing paper. F.J.A.G. and F.M.A.: conducted experiments, analyzed and interpretation of data, feedback on the paper. J.M.G.: feedback on the paper. J.H.M., J.S., and F.B.O.: interpretation of data, feedback on the paper. All authors read and approved the final manuscript., Heart rate variability (HRV) is a valid and non-invasive indicator of cardiac autonomic nervous system functioning. Short-term HRV recordings (e.g., 10 min long) produce data that usually is manually processed. Researcher subjective decision-making on data processing could produce inter- or intraresearcher differences whose magnitude has not been previously quantified in three independent human cohorts. This study examines the inter- and intra-researcher reproducibility of HRV parameters (i.e., the influence of R–R interval selection by different researchers and by the same researcher in different moments on the quantification of HRV parameters, respectively) derived from short-term recordings in a cohort of children with overweight/obesity, young adults and middle-age adults. Participants were recruited from 3 different studies: 107 children (10.03 ± 1.13 years, 58% male), 132 young adults (22.22 ± 2.20 years, 33% males) and 73 middle-aged adults (53.62 ± 5.18 years, 48% males). HRV was measured using a Polar RS800CX heart rate monitor. The intraclass correlation coefficient (ICC) ranged from 0.703 to 0.989 and from 0.950 to 0.998 for inter-and intra-researcher reproducibility, respectively. Limits of agreement for HRV parameters were higher for the interresearcher processing compared with the intra-researcher processing. On average, the intraresearcher differences were 31%, 62%, and 80% smaller than the inter-researchers differences based on Coefficient of Variation in children, young and middle-aged adults, respectively. Our study provides the quantification of the inter-researcher and intra-researcher differences in three independent human cohorts, which could elicit some clinical relevant differences for HRV parameters. Based on our findings, we recommend the HRV data signal processing to be performed always by the same trained researcher and we postulate a development of algorithms for an automatic ECG selection., Spanish Ministry of Economy and Competitiveness DEP2013-47540 DEP2016-79512-R PTA 12264-I, Spanish Ministry of Education, Culture and Sport FPU 16/02760 FPU15/02645 FPU15/04059 FPU14/06837 FPU14/04172, Unit of Excellence on Exercise and Health (UCEES), EXERNET Research Network on Exercise and Health in Special Populations DEP2005-00046/ACTI, Unit of Excellence in Sport and Health (UCEES) - University of Granada, Junta de Andalucía, European Union (EU) SOMM17/6107/UGR

Resistance training (RT) is a powerful first-line intervention for the management of type 2 diabetes mellitus (T2DM). Nonetheless, the effects of the most frequent RT (hypertrophy training [HT] and muscular endurance training [MERT]) employed for the management of T2DM, and which type of RT might exert superior effects, remain elusive. Thus, this review aims to assess the effects of HT and MERT on glycaemic control, physical fitness, body composition, lipid profile, blood pressure, C-reactive protein, and quality of life in patients with T2DM; to analyse which particular RT is more effective; to assess the effects of general RT; and to identify RT components, characteristics of patients, and medications that could mediate the effects of RT. Randomized controlled trials (RCT) and non-RCT (RT≥ 4 weeks) in adults with T2DM were selected. Both HT and MERT improved HbA1c, insulin levels and sensitivity, muscle strength, body mass index, waist circumference, and fat mass. Additionally, HT improved glucose, cardiorespiratory fitness, fat percentage, lean body mass, lipid profile, systolic blood pressure, and C-reactive protein, and MERT improved weight. Overall, HT and MERT exert beneficial effects well comparable with aerobic training. Both types of RT can be used as potent therapeutic interventions for the management of T2DM depending on patients' limitations/preferences.

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

Neck adipose tissue (NAT) volume increases with general adiposity, with fat accumulating in different neck tissue compartments. In patients with certain malignant/benign tumours, the accumulation of NAT, and certain NAT distributions, have been associated with cardiometabolic risk (CMR). However, it is unknown whether the same relationships exist in healthy people, and whether NAT accumulation and distribution are related to the inflammatory status.In this cross-sectional study, 139 young healthy adults (68% women) underwent a computed tomography scan to quantify the volume of compartmental (i.e., subcutaneous, intermuscular and perivertebral) and total NAT at the height of vertebra C5. Anthropometric indicators were measured, and body composition determined using dual energy X-ray absorptiometry. Information on CMR factors (i.e., blood glycaemic and lipid markers, blood pressure and physical fitness) was also gathered, and a CMR score calculated. Several plasma cytokines and serum components of the innate immune system were measured to determine the inflammatory status.Compartmental and total NAT volumes were directly related to body mass index (BMI), and lean, fat, and visceral adipose tissue (VAT) masses (all, P ≤ 0.05). Larger compartmental (especially intermuscular) and total NAT volumes were directly associated with the CMR score, several CMR factors (i.e., glycaemic and lipid markers and blood pressure), and the C3, C4 and leptin concentrations. They were, however, inversely correlated with the CMR factors high density lipoprotein-cholesterol (HDL-C) and physical fitness, and with the adiponectin concentration (all P ≤ 0.05). Several of these associations remained statistically significant (P ≤ 0.05) after adjustment for BMI, body fat percentage or VAT mass. Overall, results did not change after applying false discovery rate correction.NAT volume and its distribution among different tissue compartments is associated with the CMR and inflammatory profile of young healthy adults. Total NAT volume appears to be as valuable as VAT mass in terms of predicting CMR and inflammatory status.

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.

The authors would like to express their gratitude to Imran Khan for the language and editing assistance., Obesity and sleep disturbances are both related to endocrine and metabolic alterations, cardiovascular disease, and impaired daytime functioning and mood. However, the bidirectional relationship between these conditions and the underlying mechanisms still remain unclear. This study aimed to investigate the potential association of anthropometric and body composition parameters with sleep in young adults, considering the mediating role of sedentariness, physical activity, and diet. A total of 187 adults aged 18–25 (35.29% men) participated in the study. Body mass index (BMI), waist–hip ratio, and waist–height ratio were calculated, and a dual-energy X-ray absorptiometry scanner was used to assess body composition. Sedentary time and physical activity, as well as sleep duration and quality, were objectively and subjectively measured using accelerometry and the Pittsburgh Sleep Quality Index. An inverse association was found between BMI and total sleep time (β = −0.165, p = 0.029). Waist–hip ratio and lean mass index were also negatively associated with total sleep time (β = −0.222, p = 0.007, and β = −0.219, p = 0.004) and sleep efficiency (β = −0.174, p = 0.037, and β = −0.188, p = 0.013). Sedentary time moderated by sex explained the association of BMI with total sleep time such that a high BMI was related to higher sedentariness in men which, in turn, was significantly associated with shorter sleep duration. Sedentary time is, therefore, a link/risk factor mediating the association of high BMI with short sleep duration in healthy young men., Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III PI13/01393, Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad DEP2016-79512-R, Spanish Ministry of Economy and Competitiveness via European Regional Development Funds (ERDF), Spanish Government FPU16/01093, Spanish Ministry of Education and Science (Red EXERNET) DEP2005-00046, 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), Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR

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.

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.

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.

The present study examines whether the daily rhythm of distal skin temperature (DST) is associated with brown adipose tissue (BAT) metabolism as determined by 18F-fluorodeoxyglucose (18F-FDG) uptake in young adults. Using a wireless thermometer (iButton) worn on the nondominant wrist, DST was measured in 77 subjects (26% male; age 22 ± 2 years; body mass index 25.2 ± 4.8 kg/m2) for 7 consecutive days. The temperatures to which they were habitually exposed over the day were also recorded. The interday stability of DST was calculated from the collected data, along with the intraday variability and relative amplitude; the mean temperature of the 5 and 10 consecutive hours with the maximum and minimum DST values, respectively; and when these hours occurred. Following exposure to cold, BAT volume and mean and peak standardized 18F-FDG uptake (SUVmean and SUVpeak) were determined for each subject via static 18F-FDG positron emission tomography/computed tomography scanning. Relative amplitude and the time at which the 10 consecutive hours of minimum DST values occurred were positively associated with BAT volume, SUVmean, and SUVpeak ( p ≤ 0.02), whereas the mean DST of that period was inversely associated with the latter BAT variables ( p ≤ 0.01). The interday stability and intraday variability of the DST were also associated (directly and inversely, respectively) with BAT SUVpeak ( p ≤ 0.02 for both). All of these associations disappeared, however, when the analyses were adjusted for the ambient temperature to which the subjects were habitually exposed. Thus, the relationship between the daily rhythm of DST and BAT activity estimated by 18F-FDG uptake is masked by environmental and likely behavioral factors. Of note is that those participants exposed to the lowest ambient temperature showed 3 to 5 times more BAT volume and activity compared with subjects who were exposed to a warmer ambient temperature.

Humans have metabolically active brown adipose tissue (BAT). However, what is the relation between exercise or physical activity with this tissue remains controversial. Therefore, the main aim of the present study is to examine whether cardiorespiratory fitness and muscular strength are associated with brown adipose tissue (BAT) volume and activity after exposure to cold in young, sedentary adults. Cardiorespiratory fitness was determined in 119 young, healthy, sedentary adults (68% women, age 21.9 ± 2.1 years, body mass index 25 ± 4.8 kg/m2) via the maximum treadmill exercise test, and their muscular strength assessed by the handgrip strength test and the 1-repetition maximum bench and leg press tests. Some days later, all subjects were exposed to 2 h of personalized exposure to cold and their cold-induced BAT volume and activity determined by a combination of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography scan. Cardiorespiratory fitness was associated with neither the BAT volume nor BAT activity (P ≥ 0.05). However, handgrip strength with respect to lean body mass was positively (though weakly) associated with BAT activity as represented by the 18F-FDG mean standardised uptake value (SUV) (β = 3.595, R2 = 0.039, P = 0.031) and SUVpeak value (β = 15.314, R2 = 0.037, P = 0.035). The above relationships remained after adjusting for several confounders. No other associations were found. Handgrip strength with respect to lean body mass is positively associated with BAT activity (SUVmean and SUVpeak) in young adults after exposure to cold - but only weakly. Further studies are needed to reveal the relationship between muscular fitness and human BAT characteristics., This study was supported by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), Retos de la Sociedad (DEP2016-79512-R) and European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU13/04365 and FPU14/04172), 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 (ERDF: SOMM17/6107/UGR).

Background Brown adipose tissue (BAT) seems to play a role in bone morphogenesis. A negative association has been reported between BAT and bone mineral density (BMD) in women, but not in men. A panel of experts has recently published a set of recommendations for BAT assessment, and thus, to re-address previously reported associations is needed. This study aimed to investigate the association between cold-induced BAT (18) F-Fluorodeoxyglucose (F-18-FDG) uptake and BMD in young healthy adults.Methods Ninety-eight healthy adults (68 women; 22 +/- 2.2 years old; 24.3 +/- 4.5 kg/m(2)) cold-induced BAT was assessed by means of an F-18-FDG positron emission tomography-computed tomography (PET-CT) scan preceded by a personalized cold stimulation. The cold exposure consisted in 2 h in a mild cold room at 19.5-20 degrees C wearing a water perfused cooling vest set 4 degrees C above the individual shivering threshold. Total body and lumbar spine BMD were assessed by a whole-body DXA scan.Results We found no association between BMD and cold-induced BAT volume, mean, and maximal activity (all P>0.1) in neither young and healthy men nor women. These results remained unchanged when adjusting by height, by body composition, and by objectively assessed physical activity. Sensitivity analyses using the criteria to quantify cold-induced BAT-related parameters applied in previous studies did not change the results.Conclusions In summary, our study shows that there is no association between cold-induced BAT and BMD in young healthy adults. Moreover, our data support the notion that previously shown associations between BAT and BMD in healthy non-calorically restricted individuals, could be driven by methodological issues related to BAT assessment and/or sample size limitations.

The present work examines the relationships of objectively measured sedentary time and physical activity (PA) with maximal fat oxidation during exercise (MFO) and the intensity of exercise that elicits MFO (Fatmax ), in young and middle-aged men and women. A total of 121 young sedentary adults (81 women, age 22.1 ± 2.1 years, body mass index 25.2 ± 4.9 kg/m2 ) and 70 middle-aged sedentary adults (36 women, age 53.4 ± 4.9 years, body mass index 26.8 ± 3.8 kg/m2 ) participated in this cross-sectional study. PA was objectively assessed using a wrist-worn accelerometer for 7 consecutive days. Wrist accelerations were classified into sedentary time and PA of different intensity (light, moderate, vigorous, moderate-vigorous), taking into account age-specific cut-offs. MFO and Fatmax were determined for all subjects by indirect calorimetry, using a walking graded exercise test. No association was found between any of the sedentary time-related variables and MFO (all P ≥ .05). However, several sedentary time-related variables were related to FATmax in young men and women (all P ≤ .04). A positive relationship was also detected between PA and MFO in young and middle-aged women (P ≤ .05), although this became non-significant after adjustment for cardiorespiratory fitness (P > .05). The present results suggest that, depending on the characteristics of the study cohort, sedentary time, and PA time may be related to MFO and FATmax during exercise. Future longitudinal and intervention studies are warranted to better understand the role of sedentary time and PA in metabolic flexibility during exercise.

Humans have metabolically active brown adipose tissue (BAT). However, what is the relation between exercise or physical activity with this tissue remains controversial. Therefore, the main aim of the present study is to examine whether cardiorespiratory fitness and muscular strength are associated with brown adipose tissue (BAT) volume and activity after exposure to cold in young, sedentary adults. Cardiorespiratory fitness was determined in 119 young, healthy, sedentary adults (68% women, age 21.9 ± 2.1 years, body mass index 25 ± 4.8 kg/m2) via the maximum treadmill exercise test, and their muscular strength assessed by the handgrip strength test and the 1-repetition maximum bench and leg press tests. Some days later, all subjects were exposed to 2 h of personalized exposure to cold and their cold-induced BAT volume and activity determined by a combination of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography scan. Cardiorespiratory fitness was associated with neither the BAT volume nor BAT activity (P ≥ 0.05). However, handgrip strength with respect to lean body mass was positively (though weakly) associated with BAT activity as represented by the 18F-FDG mean standardised uptake value (SUV) (β = 3.595, R2 = 0.039, P = 0.031) and SUVpeak value (β = 15.314, R2 = 0.037, P = 0.035). The above relationships remained after adjusting for several confounders. No other associations were found. Handgrip strength with respect to lean body mass is positively associated with BAT activity (SUVmean and SUVpeak) in young adults after exposure to cold - but only weakly. Further studies are needed to reveal the relationship between muscular fitness and human BAT characteristics.

This study is part of a Ph.D. thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spain., Currently, 18 [F]-Fluorodeoxyglucose (18F-FDG) in combination with a positron emission tomography/computed tomography (PET/CT) scan analysis is the most commonly used method to quantify human BAT volume and activity. However, this technique presents several drawbacks which negatively affect participant's health. The aim of the present work is to determine whether supraclavicular skin temperature can be used as an indirect marker of cold-induced BAT and skeletal muscle 18F-FDG uptake in adults, while taking into account body composition. We performed a personalized cooling protocol just before an 18F-FDG-PET/CT scan, and we measured supraclavicular skin temperature before (in warm conditions) and after the cooling protocol in 88 adults (n = 57 women, mean age: 21.9 ± 2.1 years old, body mass index: 24.5 ± 4.3 km/m2). We found that supraclavicular skin temperature at the warm and cold periods was weakly and positively associated with BAT activity (SUVmean and SUVpeak: β = 3.000; R2 = 0.072; P = 0.022 and β = 2.448; R2 = 0.060; P = 0.021), but not with skeletal muscle 18F-FDG uptake, after controlling for body composition. We performed further analyses and the positive associations persisted only in the group of women. In conclusion, supraclavicular skin temperature in warm and cold conditions seems to be related with cold-induced 18F-FDG uptake by BAT only in women, although the low explained variance of these associations means that there are other factors involved in the supraclavicular skin temperature., 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, 14/04172, and 16/05159), by the Fundación Iberoamericana de Nutrición (FINUT), by the Redes temáticas de investigación cooperativa RETIC (Red SAMID RD16/0022), by AstraZeneca HealthCare Foundation and by 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).