Brown and Beige Adipose Tissues in Health and Disease.

Brown and beige adipocytes arise from distinct developmental origins. Brown adipose tissue (BAT) develops embryonically from precursors that also give to skeletal muscle. Beige fat develops postnatally and is highly inducible. Beige fat recruitment is mediated by multiple mechanisms, including de novo beige adipogenesis and white-to-brown adipocyte transdifferentiaiton. Beige precursors reside around vasculatures, and proliferate and differentiate into beige adipocytes. PDGFRα+Ebf2+ precursors are restricted to beige lineage cells, while another PDGFRα+ subset gives rise to beige adipocytes, white adipocytes, or fibrogenic cells. White adipocytes can be reprogramed and transdifferentiated into beige adipocytes. Brown and beige adipocytes display many similar properties, including multilocular lipid droplets, dense mitochondria, and expression of UCP1. UCP1-mediated thermogenesis is a hallmark of brown/beige adipocytes, albeit UCP1-independent thermogenesis also occurs. Development, maintenance, and activation of BAT/beige fat are guided by genetic and epigenetic programs. Numerous transcriptional factors and coactivators act coordinately to promote BAT/beige fat thermogenesis. Epigenetic reprograming influences expression of brown/beige adipocyte-selective genes. BAT/beige fat is regulated by neuronal, hormonal, and immune mechanisms. Hypothalamic thermal circuits define the temperature setpoint that guides BAT/beige fat activity. Metabolic hormones, paracrine/autocrine factors, and various immune cells also play a critical role in regulating BAT/beige fat functions. BAT and beige fat defend temperature homeostasis, and regulate body weight and glucose and lipid metabolism. Obesity is associated with brown/beige fat deficiency, and reactivation of brown/beige fat provides metabolic health benefits in some patients. Pharmacological activation of BAT/beige fat may hold promise for combating metabolic diseases. © 2017 American Physiological Society. Compr Physiol 7:1281-1306, 2017.