Induction of thermogenic adipocytes: molecular targets and thermogenic small molecules

Adipose tissue is a central metabolic organ that controls energy homeostasis of the whole body. White adipose tissue (WAT) stores excess energy in the form of triglycerides, whereas brown adipose tissue (BAT) dissipates energy in the form of heat through mitochondrial uncoupling protein 1 (Ucp1). A newly identified adipose tissue called ‘beige fat’ (BAT-like) is produced through a process called WAT browning. This tissue mainly resides in WAT depots and displays intermediate characteristics of both WAT and BAT. Since the recent discovery of BAT in the human body, along with the identification of molecular targets for BAT activation, stimulating energy expenditure has been considered as a great strategy to treat human obesity and metabolic diseases. Here we summarize recent findings regarding molecular targets and thermogenic small molecules that can stimulate BAT and increase energy expenditure, with an emphasis on possible therapeutic applications in humans. Types of fat tissue called “brown fat” and “beige fat” could be stimulated by drug treatment to burn off excess energy supplies as heat. Beige fat is a recently discovered heat-generating intermediate between white fat, which stores energy as fat deposits, and brown fat, which converts nutrients into heat. Kye Won Park and colleagues at Sungkyunkwan University in South Korea, with co-workers in USA, review the variety of natural and synthetic small molecules found to promote the conversion of white fat into beige fat, or to increase heat generation in brown fat. These molecules are potential therapeutic agents for treating obesity and overweight. They may also guide the synthesis of similar but more clinically suitable alternatives. The review considers the mechanisms behind the molecules' effects, and highlights issues requiring further research.