Brown adipose tissue and the genetics of obesity

Obesity is associated with a number of metabolic diseases and various cancers. At the biological level, obesity is caused by a shift in the body's energy balance toward energy abundance. The main function of one type of adipocyte called brown adipocytes, found in brown adipose tissue (BAT), is to dissipate energy as heat-generated through action of uncoupling protein 1 (UCP1)-in response to certain physiological stimuli, a process called adaptive thermogenesis. A second type of UCP1-positive thermogenic adipocyte appears in the subcutaneous white adipose tissue (WAT) in response to chronic exposure to cold or to agonists for β₃-adrenergic receptor (β₃-AR) and peroxisome proliferator-activated receptor γ (PPARγ); these are called beige/brite adipocytes. Brown and beige/brite cells originate from different developmental lineages and the energy expenditure ability of these cells gave us great hope that BAT can be manipulated to treat obesity. Here, I review the progress made thus far in understanding the developmental origins of brown and beige cells and the molecular regulation of BAT-mediated thermogenesis, studied in various knockout and transgenic mouse models.