Brown adipose tissue as a secretory organ

Key Points The activity of brown adipose tissue (BAT) is associated with protection against obesity and associated metabolic alterations such as insulin resistance Experimental evidence indicates that BAT has systemic effects by secreting regulatory molecules in addition to its capacity to use metabolic substrates for thermogenesis Brown and beige adipocytes secrete multiple autocrine and paracrine factors that control expansion and activity of BAT and the extent of browning of white adipose tissue BAT releases endocrine factors that can target peripheral tissues such as white adipose tissue, liver, pancreas, heart and bone, as well as affect systemic metabolism by interacting with the CNS In addition to undergoing adaptive thermogenesis, brown adipose tissue secretes a number of adipokines that can influence systemic metabolism. In this Review, Villarroya and colleagues discuss the current evidence for these so-called 'batokines' and how they might influence whole-body metabolic health. Brown adipose tissue (BAT) is the main site of adaptive thermogenesis and experimental studies have associated BAT activity with protection against obesity and metabolic diseases, such as type 2 diabetes mellitus and dyslipidaemia. Active BAT is present in adult humans and its activity is impaired in patients with obesity. The ability of BAT to protect against chronic metabolic disease has traditionally been attributed to its capacity to utilize glucose and lipids for thermogenesis. However, BAT might also have a secretory role, which could contribute to the systemic consequences of BAT activity. Several BAT-derived molecules that act in a paracrine or autocrine manner have been identified. Most of these factors promote hypertrophy and hyperplasia of BAT, vascularization, innervation and blood flow, processes that are all associated with BAT recruitment when thermogenic activity is enhanced. Additionally, BAT can release regulatory molecules that act on other tissues and organs. This secretory capacity of BAT is thought to be involved in the beneficial effects of BAT transplantation in rodents. Fibroblast growth factor 21, IL-6 and neuregulin 4 are among the first BAT-derived endocrine factors to be identified. In this Review, we discuss the current understanding of the regulatory molecules (the so-called brown adipokines or batokines) that are released by BAT that influence systemic metabolism and convey the beneficial metabolic effects of BAT activation. The identificati