Fat cells directly sense temperature to activate thermogenesis.

Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1. This nonshivering thermogenesis is crucial for mammals as a defense against cold and obesity/diabetes. Cold is known to act indirectly through the sympathetic nervous systems and β-adrenergic signaling, but here we report that cool temperature (27-33 °C) can directly activate a thermogenic gene program in adipocytes in a cell-autonomous manner. White and beige fat cells respond to cool temperatures, but classic brown fat cells do not. Importantly, this activation in isolated cells is independent of the canonical cAMP/Protein Kinase A/cAMP response element-binding protein pathway downstream of the β-adrenergic receptors. These findings provide an unusual insight into the role of adipose tissues in thermoregulation, as well as an alternative way to target nonshivering thermogenesis for treatment of obesity and metabolic diseases.