Endocrine Abstracts

Three major observations triggered a revitalized interest in the role of brown fat in energy balance and the metabolic benefits of this thermogenic tissue in humans. Firstly, progenitors of brown adipocytes derive from the muscle lineage whereas recruitable brown-like adipocytes in white fat, termed brite (brown-in-white), can be of other developmental origin. Secondly, healthy adult humans have metabolically powerful brown/brite fat that is activated by acute cold exposure, β3-adrenergic receptor agonist treatment, or after ingestion of a meal. Thirdly, cold-induced metabolic activity of brown/brite fat in humans is negatively associated with body mass index and age, and is recruitable by cold-acclimation. Based on these findings human brown/brite fat has been reconsidered as a target for pharmacological or nutritional interventions in obese and diabetic subjects. The beneficial effects of brown/brite fat are attributed to the high capacity of brown/brite adipocytes to dissipate heat. Thermogenic capacity in these cells is determined by high lipolytic capacity, extraordinary mitochondrial density and expression of uncoupling protein 1 (UCP1). Located in the inner mitochondrial membrane, UCP1 is constitutively inactive, but upon lipolytic release of fatty acids dissipates proton-motive force as heat thereby causing extraordinary mitochondrial respiration rates. Enormous efforts are currently undertaken to identify treatments that stimulate the formation and maintenance of thermogenic brown/brite adipocytes, and activate UCP1 in these cells. Release of noradrenaline from sympathetic varicosities is the physiological trigger of UCP1 activation in brown/brite fat, but also de novo recruitment of thermogenic capacity. However, sympathomimetics selectively activating brown/brite fat thermogenesis without detrimental cardiovascular side-effects are currently not available. Therefore, the pros and cons for a significant role of brown/brite fat in human energy balance regulation and the evidence for non-adrenergic activators of brown fat thermogenesis will be critically addressed.