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Omega-6 and omega-3 oxylipins may be surrogate markers of systemic inflammation, which is one of the triggers for the development of cardiometabolic disorders. In the current study, we investigated the relationship between plasma levels of omega-6 and omega-3 oxylipins with body composition and cardiometabolic risk factors in middle-aged adults. Seventy-two 72 middle-aged adults (39 women; 53.6±5.1 years old; 26.7±3.8 kg/m2) were included in this cross-sectional study. Plasma levels of omega-6 and omega-3 fatty acids and oxylipins were determined using targeted lipidomic. Body composition, dietary intake, and cardiometabolic risk factors were assessed with standard methods. The plasma levels of the omega-6 fatty acids and derived oxylipins, the hydroxyeicosatetraenoic acids (HETEs; arachidonic acid (AA)-derived oxylipins) and dihydroxy-eicosatrienoic acids (DiHETrEs; AA-derived oxylipins), were positively associated with glucose metabolism parameters (i.e., insulin levels and homeostatic model assessment of insulin resistance index (HOMA); all r≥0.21, P

Pre-clinical studies suggest that circulating oxylipins, i.e., the oxidation products of polyunsaturated fatty acids (PUFAs), modulate gut microbiota composition in mice, but there is no information available in humans. Therefore, this study aimed to investigate the relationship between omega-3 and omega-6 derived oxylipins plasma levels and fecal microbiota composition in a cohort of young adults. 80 young adults (74% women; 21.9 +/- 2.2 years old) were included in this cross-sectional study. Plasma levels of oxylipins were measured using liquid chromatography-tandem mass spectrometry. Fecal microbiota composition was analyzed by V3-V4 16S rRNA gene sequencing. We observed that plasma levels of omega-3 derived oxylipins were positively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho >= 0.415, p = -0.270, p = -0.263, p = -0.263, p, Spanish Ministry of Economy and Competitiveness via 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 FPU16/05159 FPU16/02828 FPU17/01523 FPU19/01609, Fundacion Iberoamericana de Nutricion (FINUT), University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), AstraZeneca, Junta de Andalucia Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR, China Scholarship Council 201707060012, Fundacion Alfonso Martin Escudero, Ministerio de Universidades y la Union Europea -NextGenerationEU RR_C_2021_04, 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

Funding: This study was funded by the University of Granada, Plan Propio de Investigación 2016- Excellence actions: Unit of Excellence on Exercise and Health (UCEES). P.C. was supported by the Margarita Salas postdoctoral grant, convened by de University of the Basque Country (UPV/EHU), funded by the Ministry of Universities of Spain and the European Union-Next Generation EU., ONCOFIT is a randomized clinical trial with a two-arm parallel design aimed at determining the influence of a multidisciplinary Prehabilitation and Postoperative Program (PPP) on post-surgery complications in patients undergoing resection of colon cancer. This intervention will include supervised physical exercise, dietary behavior change, and psychological support comparing its influence to the standard care. Primary and secondary endpoints will be assessed at baseline, at preoperative conditions, at the end of the PPP intervention (after 12 weeks) and 1-year post-surgery, and will include: post-surgery complications (primary endpoint); prolonged hospital length of stay; readmissions and emergency department call within 1-year after surgery; functional capacity; patient reported outcome measures targeted; anthropometry and body composition; clinical/tumor parameters; physical activity levels and sedentariness; dietary habits; other unhealthy habits; sleep quality; and fecal microbiota diversity and composition. Considering the feasibility of the present intervention in a real-life scenario, ONCOFIT will contribute to the standardization of a cost-effective strategy for preventing and improving health-related consequences in patients undergoing resection of colon cancer with an important clinical and economic impact, not only in the scientific community, but also in clinical practice., University of Granada, Plan Propio de Investigación 2016- Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Margarita Salas postdoctoral grant, convened by de University of the Basque Country (UPV/EHU), funded by the Ministry of Universities of Spain and the European Union-Next Generation EU

Introduction: Vitamin D – concretely its active form 1,25-dihydroxyvitamin D (1,25(OH)2D) – maintains several physiological processes. Oxylipins are oxidized lipids derived from ω-6 and ω-3 polyunsaturated fatty acids involved in inflammation. Little is known about the association of 1,25(OH)2D with inflammatory parameters in middle-aged populations – who could be at risk of vitamin D deficiency –. The aim of this study was to investigate the relationship between 1,25(OH)2D plasma levels with circulating white blood cells, platelets counts and oxylipins levels. Materials and methods: A total of 74 (53 % women) middle-aged (40–65 years old) adults were recruited for this cross-sectional study. 1,25(OH)2D plasma levels were measured using an immunochemiluminometric assay. White blood cells and platelets were analyzed by hemocytometry. ω-6 and ω-3 oxylipins plasma levels were measured using liquid chromatography - tandem mass spectrometry. Simple and multiple linear regression models, and Pearson correlation analyses, were performed to study the association of 1,25(OH)2D levels with WBC and platelets counts, and oxylipins, respectively. Results: 1,25(OH)2D plasma levels were positively related with linoleic acid-derived oxylipins and isoprostanes plasma levels, whereas an inverse relationship with dihomo-γ-linolenic acid/linoleic acid and arachidonic acid/ linoleic acid ratios was unveiled. No significant associations were observed for circulating ω-3 oxylipins, white blood cells levels or platelets count. Conclusions: Linoleic acid-derived oxylipins and isoprostanes plasma levels may be influenced by 1,25(OH)2D plasma levels. Further investigations are needed to elucidate the impact of other vitamin D forms upon circulating oxylipins levels., Spanish Government, China Scholarship Council 201607060017 201707060012

This study aimed to investigate the effects of different exercise training programs on fasting plasma levels of oxylipins, endocannabinoids (eCBs), and eCBs-like molecules in middle-aged sedentary adults. A 12-week randomized controlled trial was conducted using a parallel group design. Sixty-five middle-aged adults (40–65 years old) were randomly assigned to: (a) no exercise (control group), (b) concurrent training based on international physical activity recommendations (PAR group), (c) high-intensity interval training (HIIT group), and (d) HIIT together with whole-body electromyostimulation (HIIT + EMS group). Plasma levels of oxylipins, eCBs, and eCBs-like molecules were determined in plasma samples before and after the intervention using targeted lipidomics. Body composition was assessed through dual-energy X-ray absorptiometry, and dietary intake through a food frequency questionnaire and three nonconsecutive 24-hr recalls. The physical activity recommendations, HIIT, and HIIT-EMS groups showed decreased plasma levels of omega-6 and omega-3-derived oxylipins, and eCBs and eCBs-like molecules after 12 weeks (all Δ ≤ −0.12; all p p > .05). However, after post hoc corrections, plasma levels of anandamide and oleoylethanolamide were increased in the physical activity recommendations group compared with the control group (anandamide: Δ = 0.05 vs. −0.09; oleoylethanolamide: Δ = −0.12 vs. 0.013, all p ≤ .049). In conclusion, this study reports that a 12-week exercise training intervention, independent of the modality applied, does not modify fasting plasma levels of omega-6 and omega-3 oxylipins, eCBs, and eCBs-like molecules in middle-aged sedentary adults.

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

The study was supported by the Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad (DEP2016-79512-R to J.R.R.) and European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU 16/02828), the University of Granada 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: ref. SOMM17/6107/UGR), The Netherlands CardioVascular Research Initiative "the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences" (CVON2017-20 GENIUS-2) to P.C.N.R., and the Chinese Scholarship Council (CSC; No. 201707060012 to X.D., No. 201607060017 to W.Y.). B.M.T. is supported by an individual postdoctoral grant from the Fundacion Alfonso Martin Escudero., Context: Bile acids (BA) are known for their role in intestinal lipid absorption and can also play a role as signaling molecules to control energy metabolism. Prior evidence suggests that alterations in circulating BA levels and in the pool of circulating BA are linked to an increased risk of obesity and a higher incidence of type 2 diabetes in middleaged adults. Objective: We aimed to investigate the association between plasma levels of BA with cardiometabolic risk factors in a cohort of well-phenotyped, relatively healthy young adults. Methods: Body composition, brown adipose tissue, serum classical cardiometabolic risk factors, and a set of 8 plasma BA (including glyco-conjugated forms) in 136 young adults (age 22.1 ± 2.2 years, 67% women) were measured. Results: Plasma levels of chenodeoxycholic acid (CDCA) and glycoursodeoxycholic acid (GUDCA) were higher in men than in women, although these differences disappeared after adjusting for body fat percentage. Furthermore, cholic acid (CA), CDCA, deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA) levels were positively, yet weakly associated, with lean body mass (LBM) levels, while GDCA and glycolithocholic acid (GLCA) levels were negatively associated with 18F-fluorodeoxyglucose uptake by brown adipose tissue. Interestingly, glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), and GUDCA were positively associated with glucose and insulin serum levels, HOMA index, low-density lipoprotein cholesterol, tumor necrosis factor alpha, interleukin (IL)-2, and IL-8 levels, but negatively associated with high-density lipoprotein cholesterol, ApoA1, and adiponectin levels, yet these significant correlations partially disappeared after the inclusion of LBM as a confounder. Conclusion: Our findings indicate that plasma levels of BA might be sex dependent and are associated with cardiometabolic and inflammatory risk factors in young and relatively healthy adults., Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad DEP2016-79512-R, European Commission Spanish Government FPU 16/02828, University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGR, Netherlands CardioVascular Research Initiative "the Dutch Heart Foundation" CVON2017-20 GENIUS-2 Netherlands CardioVascular Research Initiative "Dutch Federation of University Medical Centers" CVON2017-20 GENIUS-2, Netherlands CardioVascular Research Initiative "Netherlands Organisation for Health Research and Development" CVON2017-20 GENIUS-2 Netherlands CardioVascular Research Initiative "Royal Netherlands Academy of Sciences" CVON2017-20 GENIUS-2, China Scholarship Council 201707060012 201607060017, Fundacion Alfonso Martin Escudero, Junta de Andalucia

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.

In humans, the variation in resting metabolic rate (RMR) might be associated with health-related factors, as suggested by previous studies. This study explored whether the intra-assessment RMR variability (expressed as a coefficient of variation (CV; %)) is similar in men and women and if it is similarly associated with diverse health-related factors. The RMR of 107 young, and relatively healthy adults, was assessed using indirect calorimetry. Then, the CV for volumes of oxygen consumption (VO2) and carbon dioxide production (VCO2), respiratory exchange ratio (RER), and resting energy expenditure (REE) were computed as indicators of intra-assessment RMR variability. Body composition, cardiorespiratory fitness (peak VO2 uptake), circulating cardiometabolic risk factors, and heart rate and its variability (HR and HRV) were assessed. Men presented higher CVs for VO2, VCO2, and REE (all p, Spanish Ministry of Economy and Competitiveness (DEP2016-79512-R and PTA 12264-I), Spanish Ministry of Education, Culture and Sport (FPU15/04059, FPU16/02828, and FPU 16/02760), University of Granada, Plan Propio de Investigación 2020 Programa de Contratos Puente, Grant FJC2020-044453-I MCIN/AEI/10.13039/501100011033, European Union NextGenerationEU/PRTR, NIH grant #: U01 TR002004 (REACH project), 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), Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Funds (ref. SOMM17/6107/UGR)

Background: Succinate is produced by both host and microbiota, with a key role in the interplay of immunity and metabolism and an emerging role as a biomarker for infammatory and metabolic disorders in middle-aged adults. The relationship between plasma succinate levels and cardiovascular disease (CVD) risk in young adults is unknown. Methods: Cross-sectional study in 100 (65% women) individuals aged 18–25 years from the ACTIvating Brown Adipose Tissue through Exercise (ACTIBATE) study cohort. CVD risk factors, body composition, dietary intake, basal metabolic rate, and cardiorespiratory ftness were assessed by routine methods. Plasma succinate was measured with an enzyme-based assay. Brown adipose tissue (BAT) was evaluated by positron emission tomography, and circulating oxylipins were assessed by targeted metabolomics. Fecal microbiota composition was analyzed in a sub-sample. Results: Individuals with higher succinate levels had higher levels of visceral adipose tissue (VAT) mass (+42.5%), tri‑ glycerides (+63.9%), C-reactive protein (+124.2%), diastolic blood pressure (+5.5%), and pro-infammatory omega-6 oxylipins than individuals with lower succinate levels. Succinate levels were also higher in metabolically unhealthy individuals than in healthy overweight/obese peers. Succinate levels were not associated with BAT volume or activity or with fecal microbiota composition and diversity. Conclusions: Plasma succinate levels are linked to a specifc pro-infammatory omega-6 signature pattern and higher VAT levels, and seem to refect the cardiovascular status of young adults., Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad (DEP2016-79512-R to JRR and RTI2018-093919-B to SFV), European Regional Development Funds (ERDF), Spanish Ministry of Education (FPU16/02828, FPU16/05159, FPU17/01523 and FPU19/01609), University of Granada Plan Propio de Investigación 2016-Excellence actions–Unit of Excellence on Exercise and Health (UCEES), Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF: ref. SOMM17/6107/UGR), The Spanish Ministry of Science and Innovation (PI20/00095 to VCM and PI20/00338 to JV) co-fnanced by the European Regional Development Fund (ERDF), Ramón y Cajal program (RYC2019026490-I) from the Spanish Ministry of Science and Innovation, co-fnanced by the ERDF, y Fundación Bancaria Caixa d’Estalvis i Pensions de Barcelona (HR20-00051 to S.F.-V.), The Netherlands CardioVascular Research Initiative: ‘the Dutch Heart Foundation, Dutch Federation of University Medical Centers, The Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences’ (CVON2017-20 GENIUS-2) to PCNR, Chinese Scholarship Council (CSC, No. 201707060012) to XD, Miguel Servet tenure-track program (CP10/00438 and CPII16/00008) from the Fondo de Investigación Sanitaria, co-fnanced by the ERDF, Fundación Alfonso Martin Escudero

Activation of brown adipose tissue (BAT) and promotion of white adipose tissue (WAT) browning is considered a potential tool to combat obesity and cardiometabolic disorders. The use of plant-based dietary components has become one of the most used strategies for activating BAT and promoting WAT browning in rodents. The main reason is because plant-based dietary components are usually recognized as safe when the dose is properly adjusted, and they can easily be administrated by being added to the diet or dissolved in water. The present systematic review aimed to study the effects of plant-based dietary components on activation of BAT and promotion of WAT browning in rodents. A systematic search of PubMed and Scopus (from 1978 to 2019) identified eligible studies. Studies assessing the effects of plant-based dietary components added to diet and/or water on uncoupling protein 1 (UCP1) expression in BAT and/or WAT were included. Studies that used dietary components of animal origin, did not specify the effects on UCP1, or were conducted in other species different from mice or rats were excluded. Of 3919 studies identified in the initial screening, 146 studies were finally included in the review. We found that tea extract catechins, resveratrol, capsaicin and capsinoids, cacao extract flavanols, and quercetin were the most studied components. Scientific evidence suggests that some of these dietary components activate BAT and promote WAT browning via activation of the AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) pathways. These findings reveal that there is strong scientific evidence supporting the use of plant-based dietary components to activate BAT and promote WAT browning in rodents and thus to potentially combat obesity and cardiometabolic disorders.

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.

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.

Human brown adipose tissue (BAT) has attracted clinical interest not only because it dissipates energy but also for its potential capacity to counteract obesity and related metabolic disorders (e.g., insulin resistance and dyslipidemia). Cold exposure is the most powerful stimulus for activating and recruiting BAT, and this stimulatory effect is mediated by the transient receptor potential (TRP) channels. BAT can also be activated by other receptors such as the G-protein-coupled bile acid receptor 1 (GPBAR1) or beta-adrenergic receptors. Interestingly, these receptors also interact with several dietary components; in particular, capsinoids and tea catechins appear to mimic the effects of cold through a TRP-BAT axis, and they consequently seem to decrease body fat and improve metabolic blood parameters. This systematic review critically addresses the evidence behind the available human studies analyzing the effect of several dietary components (e.g., capsinoids, tea catechins, and ephedrine) on BAT activity. Even though the results of these studies are consistent with the outcomes of preclinical models, the lack of robust study designs makes it impossible to confirm the BAT-activation capacity of the specified dietary components. Further investigation into the effects of dietary components on BAT is warranted to clarify to what extent these components could serve as a powerful strategy to treat obesity and related metabolic disorders.

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.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

Human brown adipose tissue (BAT) was re-discovered in 2009 by several independent groups, who showed that it is present and active in adults, as judged from the profound uptake of the glucose analogue radiotracer 18F-fluorodeoxyglucose in positron-emission tomography and computed tomography scan analysis after cold exposure. A potential clinical implication of activating BAT relates to its high metabolic activity and its potential role in stimulating energy expenditure (i.e. resting energy expenditure, meal-induced thermogenesis, and cold-induced thermogenesis), which makes it an attractive target to reduce adiposity. Moreover, due to its ability to oxidise glucose and lipids, BAT activation may also potentially exert beneficial metabolic and cardiovascular effects through reducing glucose and lipid levels, respectively. This review describes the potential role of human BAT in the prevention and treatment of obesity, metabolism, and cardiovascular disease focusing on its impact on energy expenditure and management of body fat accumulation as well as on glucose and lipid metabolism. This article also summarises the strategies that are currently being studied to activate human BAT.