Hypothalamus and thermogenesis: Heating the BAT, browning the WAT

•The hypothalamus regulates brown fat thermogenesis and browning of white fat.•Hormones signal at the hypothalamus to regulate BAT and WAT through the SNS.•The AMPK(VMH)-SNS-BAT is a canonical pathway regulating energy balance.•Targeting BAT or browning of WAT might be suitable strategies to treat obesity.

Brown adipose tissue (BAT) has been also considered as the main thermogenic organ responsible of maintenance body temperature through heat production. However, a new type of thermogenic fat has been characterized during the last years, the beige or brite fat, that is developed from white adipose tissue (WAT) in response to different stimuli by a process known as browning. The activities of brown and beige adipocytes ameliorate metabolic disease, including obesity in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease. The hypothalamus is the main central place orchestrating the outflow signals that drive the sympathetic nerve activity to BAT and WAT, controlling heat production and energy homeostasis. Recent data have revealed new hypothalamic molecular mechanisms, such as hypothalamic AMP-activated protein kinase (AMPK), that control both thermogenesis and browning. This review provides an overview of the factors influencing BAT and WAT thermogenesis, with special focus on the integration of peripheral information on hypothalamic circuits controlling thermoregulation.