Brown adipose tissue thermogenesis

Human brown adipose tissue (BAT) has emerged as a metabolically dynamic organ with the potential to influence thermoregulation, substrate utilization, and cardiometabolic health. This review synthesizes current knowledge on the biomolecular features of human BAT, physiological and pharmacological strategies to stimulate energy dissipation, the tools used to measure its function in vivo, and its role in thermoregulation and metabolic disease. Molecular profiling reveals that human BAT contains heterogeneous thermogenic adipocytes with multilocular lipid droplets, rich innervation and vascularization, compartmentalized mitochondria, and-beyond its hallmark expression of uncoupling protein 1 (UCP1)-the capacity to recruit broader oxidative and futile-cycle pathways. Anatomically, BAT is distributed across several depots with distinct recruitment potential that varies widely between individuals. Cold exposure remains the most potent activator, although nutritional and pharmacological stimuli can also modulate BAT activity. Advances in imaging have expanded the ability to quantify BAT thermogenesis, from gold-standard [¹⁵O]O₂ and [¹¹C]acetate PET to multi-tracer and multimodal approaches aimed at capturing oxidative flux and heat production. These methods indicate that human BAT contributes modestly to lipid and glucose clearance and whole-body energy expenditure, yet spontaneous uptake of [¹⁸F]fluorodeoxyglucose remains consistently associated with lower adiposity and reduced cardiometabolic risk. Major uncertainties persist regarding the true thermogenic capacity of human BAT, the functional relevance of beige adipocytes, the balance between UCP1-dependent and UCP1-independent heat-producing pathways, and the most reliable metrics of in vivo activation. Addressing these known unknowns will require integrated, multimodal approaches to define when, where, and how human BAT contributes to metabolic health.