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Brown adipose tissue (BAT) stands out as the sole tissue able to substantially expend energy by leveraging uncoupling protein 1 (UCP1) to increase proton permeability through the inner mitochondrial membrane. [...]

Aim: Pharmacological stimulation of human brown adipose tissue (BAT) has been hindered by ineffective activation or undesirable off‐target effects. Oral administration of the maximal allowable dose of mirabegron (200 mg), a β3‐adrenergic receptor (β3‐AR) agonist, has been effective in stimulating BAT thermogenesis and whole‐body energy expenditure. However, this has been accompanied by undesirable cardiovascular effects. Therefore, we hypothesized that combining mirabegron with a β1‐AR antagonist could suppress these unwanted effects and increase the stimulation of the β3‐AR and β2‐AR in BAT. Methods: We performed a randomized crossover trial (NCT04823442) in 8 lean men. Mirabegron (200 mg) was administered orally with or without the β1‐AR antagonist bisoprolol (10 mg). Dynamic [11C]‐acetate and 2‐deoxy‐2‐[18F]fluoro‐d‐glucose PET/CT scans were performed sequentially after oral administration of mirabegron ± bisoprolol. Results: Compared to room temperature, mirabegron alone increased BAT oxidative metabolism (0.84 ± 0.46 vs. 1.79 ± 0.91 min−1, p = 0.0433), but not when combined with bisoprolol. The metabolic rate of glucose in BAT, measured using [18F]FDG PET, was significantly higher with mirabegron than mirabegron with bisoprolol (24 ± 10 vs. 16 ± 8 nmol/g/min, p = 0.0284). Bisoprolol inhibited the mirabegron‐induced increase in systolic blood pressure and heart rate. Conclusion: The administration of bisoprolol decreases the adverse cardiovascular effects of mirabegron. However, the provided dose also blunted the mirabegron‐stimulated increase in BAT lipolysis, thermogenesis, and glucose uptake. The attenuation in BAT blood flow induced by the large dose of bisoprolol may have limited BAT thermogenesis. [ABSTRACT FROM AUTHOR]

Relative Energy Deficiency in Sport (RED-S) syndrome is associated with undesirable health and performance outcomes. The aetiology of RED-S syndrome is low energy availability (LEA). LEA has been reported in male athletes in various sports, but there is little information in team sports. Therefore, the aims of this study were to assess the point-prevalence of surrogate markers of LEA in elite male volleyball players and examine the association between low and normal total-testosterone (TES) on endocrine markers, resting metabolic rate, bone mineral density (BMD), and history of injury/illness. Using a cross-sectional design, 22 elite male volleyball players underwent anthropometric, dual-energy X-ray absorptiometry (DEXA or DXA) and resting metabolic rate testing, bloodwork, dietary analysis, the three-factor eating questionnaire–R18, injury/illness questionnaire and Victorian Institute of Sport Assessment – patellar tendon questionnaire. The primary finding of this investigation was that 36% of athletes had ≥2 surrogate markers of LEA. Although fasted insulin was lower and cortisol was higher in players with low-total TES, low BMD, low RMR and various other endocrine markers linked to LEA were not observed. More research is required to define surrogate markers of LEA in male athletes. HIGHLIGHTS Thirty-six percent of volleyball players had ≥2 surrogate markers of LEA. The Cunningham, 1991 predictive RMR equation and/or the cut-off point (<0.9) may be unsuitable for detecting energy conservation associated with LEA in large male athletes. There was no association between total-TES and risk of bone stress injury, illness and patellar tendinopathy. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by the central nervous and endocrine systems and circulating metabolites, the plausible roles of this tissue in human thermoregulation, energy balance, and cardiometabolic disorders, and the current knowledge on its pharmacological stimulation in humans. The current definition and measurement of BAT in human studies relies almost exclusively on BAT glucose uptake from positron emission tomography with 18F-fluorodeoxiglucose, which can be dissociated from BAT thermogenic activity, as for example in insulin-resistant states. The most important energy substrate for BAT thermogenesis is its intracellular fatty acid content mobilized from sympathetic stimulation of intracellular triglyceride lipolysis. This lipolytic BAT response is intertwined with that of white adipose (WAT) and other metabolic tissues, and cannot be independently stimulated with the drugs tested thus far. BAT is an interesting and biologically plausible target that has yet to be fully and selectively activated to increase the body's thermogenic response and shift energy balance. The field of human BAT research is in need of methods able to directly, specifically, and reliably measure BAT thermogenic capacity while also tracking the related thermogenic responses in WAT and other tissues. Until this is achieved, uncertainty will remain about the role played by this fascinating tissue in human cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) is vital for proper thermogenesis during cold exposure in rodents, but until recently its presence in adult humans and its contribution to human metabolism were thought to be mini-mal or insignificant. Recent studies using PET with (18) F-fluorodeoxyglucose ((18) FDG) have shown the presence of BAT in adult humans. However, whether BAT contributes to cold-induced nonshivering thermogenesis in humans has not been proven. Using PET with (11) C-acetate, (18) FDG, and (18) F-fluoro-thiaheptadecanoic acid ((18) FTHA), a fatty acid tracer, we have quantified BAT oxidative metabolism and glucose and nonesterified fatty acid (NEFA) turnover in 6 healthy men under controlled cold exposure conditions. All subjects displayed substantial NEFA and glucose uptake upon cold exposure. Furthermore, we demonstrated cold-induced activation of oxidative metabolism in BAT, but not in adjoining skeletal muscles and subcutaneous adipose tissue. This activation was associated with an increase in total energy expenditure. We found an inverse relationship between BAT activity and shivering. We also observed an increase in BAT radio density upon cold exposure, indicating reduced BAT triglyceride content. In sum, our study provides evidence that BAT acts as a nonshivering thermogenesis effector in humans., Introduction Brown adipose tissue (BAT) is a specialized tissue whose function is to produce heat (1), (2). Its thermogenic capacity is such that it allows mammals to live below thermoneutral [...]

Childhood obesity is a growing worldwide problem. In adults, lower cold-induced brown adipose tissue (BAT) activity is linked to obesity and metabolic dysfunction; this relationship remains uncertain in children. In this cross-sectional study, we compared cold-induced supraclavicular (SCV) BAT activity (percent change in proton density fat fraction [PDFF]) within the SCV region after 1 h of whole-body cold exposure (18°C), using MRI in 26 boys aged 8-10 years: 13 with normal BMI and 13 with overweight/obesity. Anthropometry, body composition, hepatic fat, visceral adipose tissue (VAT), and pre- and postcold PDFF of the subcutaneous adipose tissue (SAT) in the posterior neck region and the abdomen were measured. Boys with overweight/obesity had lower cold-induced percent decline in SCV PDFF compared with those with normal BMI (1.6 ± 0.8 vs. 4.7 ± 1.2%, P = 0.044). SCV PDFF declined significantly in boys with normal BMI (2.7 ± 0.7%, P = 0.003) but not in boys with overweight/obesity (1.1 ± 0.5%, P = 0.053). No cold-induced changes in the PDFF of either neck SAT (-0.89 ± 0.7%, P = 0.250, vs. 0.37 ± 0.3%, P = 0.230) or abdominal SAT (-0.39 ± 0.5%, P = 0.409, and 0.25 ± 0.2%, P = 0.139, for normal BMI and overweight/obesity groups, respectively) were seen. The cold-induced percent decline in SCV PDFF was inversely related to BMI (r = -0.39, P = 0.047), waist circumference (r = -0.48, P = 0.014), and VAT (r = -0.47, P = 0.014). Thus, in young boys, as in adults, BAT activity is lower in those with overweight/obesity, suggesting that restoring activity may be important for improving metabolic health. [ABSTRACT FROM AUTHOR]