Neuroendocrine Control of Brown Adipocytes: Functions, Beiging, Whitening and Autophagy

Abstract Adipose tissue has emerged as a fundamental player in metabolic and energy processes. Beyond its fat storage capacity, it displays adaptive mechanisms to react to metabolic challenges throughout life. Three types of adipocytes, white, brown and beige, share common and yet fundamentally different roles and molecular regulation. This review focuses on brain and endocrine control of the function and plasticity of brown and beige adipocytes. The involvement of brain circuits controlling brown adipocytes and thermogenesis via the sympathetic nervous system is described. This autonomic control is mainly exerted by the hypothalamus and brainstem, and noradrenaline released from sympathetic efferent postganglionic fibers interacts with brown or beige b3 adrenoreceptors (b3Adr) to trigger a cascade of events favorable to thermogenesis. Metabolic plasticity in response to environmental or hormonal cues, such as high fat diets, temperature, or hormones and aging, has been identified as a hallmark feature of brown/beige adipocytes. Besides the plastic response of WAT beiging, which is the generation of brown-like adipocytes within white adipose depots, diet-induced obesity and other cues evoke vascular remodeling and functional hypoxia in BAT leading to a whitening phenotype, characterized by mitochondrial dysfunction and loss, lipid droplet accumulation, and decreased thermogenesis. A detailed analysis of the participation of autophagy, and the endocrine signals relied by prolactin and growth hormone uncovers potential avenues of intervention to improve the metabolic function of BAT. Because BAT dysfunction in rodents is linked to fat gain, and glucose and lipid disorders, targeting BAT function and WAT beiging holds promise for obesity prevention and metabolic improvement.