Brown Adipose Tissue—A Translational Perspective

Abstract

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 (PET) with 18F-fluorodeoxiglucose ( 18FDG), 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 (TG) lipolysis. This lipolytic BAT response is intertwined with that of white adipose 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 white adipose and other tissues. Until this is achieved, uncertainty will remain about the role played by this fascinating tissue in human cardiometabolic diseases.

Muscle–fat crosstalk: effects of exercise on brown adipose tissue; what do we know?

“…browning) in mediating some of the metabolic benefits of exercise (Peppler et al, 2018;Stanford et al, 2015). Brown adipose tissue (BAT) is enriched with mitochondria and dissipates energy as heat via the mitochondrial protein, uncoupling protein-1 (UCP1), and is associated with improved metabolic health (Carpentier et al, 2022). In a recent paper published in the Journal of Physiology, Kim et al (2022) investigated the adaptations of BAT following exercise.…”

“…Another concern is the suggestion that exercise-induced UCP1 content might be driving the weight loss seen with exercise training based on increased UCP1 content and whole-body oxygen consumption and heat production (Kim et al, 2022). However, UCP1 content by itself cannot be extrapolated to thermogenesis (Carpentier et al, 2022). Moreover, heat and oxygen consumption were corrected for body mass, which can be misleading when there are substantial changes in body mass and composition, such as the large relative increase in lean mass observed in the paper by Kim et al (2022).…”

“…Moreover, heat and oxygen consumption were corrected for body mass, which can be misleading when there are substantial changes in body mass and composition, such as the large relative increase in lean mass observed in the paper by Kim et al (2022). It is well known that skeletal muscle accounts for the vast majority of whole-body energy expenditure, even under conditions associated with adipose tissue thermogenesis, such as cold exposure (Carpentier et al, 2022).…”

“…This is critical as exercise training at room temperature undoubtedly causes adaptations in white adipose tissue (WAT) and BAT in mice, as we and many others have shown (McKie et al., 2019; Peppler et al., 2018; Raun et al., 2020; Stanford et al., 2015), but more recent work has highlighted the necessity of housing mice at thermoneutrality (∼27–30°C) to more appropriately mimic human adaptations (McKie & Wright, 2021). Housing mice at thermoneutrality prevents exercise‐induced WAT browning and dramatically alters BAT thermogenesis (McKie et al., 2019; Raun et al., 2020), which recapitulates what is seen in humans (Carpentier et al., 2022; McKie & Wright, 2021). Indeed, the effects of exercise training on BAT thermogenic capacity are quite contentious with some reports suggesting that exercise training leads to BAT ‘whitening’, with reduced UCP1 content and thermogenic activity, in rodents and humans (Carpentier et al., 2022).…”

“…Perhaps the greatest concern is that mice were housed at room temperature (∼23°C) during training, which represents a thermogenic stress on mice (Carpentier et al., 2022; Kim et al., 2022; 5). This is critical as exercise training at room temperature undoubtedly causes adaptations in white adipose tissue (WAT) and BAT in mice, as we and many others have shown (McKie et al., 2019; Peppler et al., 2018; Raun et al., 2020; Stanford et al., 2015), but more recent work has highlighted the necessity of housing mice at thermoneutrality (∼27–30°C) to more appropriately mimic human adaptations (McKie & Wright, 2021).…”