DESCRIPTION (provided by applicant: Energy balance is the biological homeostasis of energy in living organisms, which means energy intake from food equals energy expenditure. When energy intake exceeds energy expenditure, excess energy will be stored as fat in adipose and other metabolic tissues, eventually leading to obesity and further development into type II diabetes. Adaptive thermogenesis represents one principle component of total energy expenditure, which refers to body heat production in response to changes of environmental temperature or diet. Brown adipose tissue is the major site of adaptive thermogenesis to dissipate energy. Recent studies indicate that brown and brown like fat (beige fat) are present in adult human, and their activities are inversely correlated with body mass index. Both cold exposure and circulating hormones can activate sympathetic nervous system to have acute and chronic impacts on brown and beige fat, although the molecular mechanisms still remain poorly understood. This Grant proposal aims to elucidate the function of a molecular switch in brown and beige fat to govern energy expenditure. In this proposal, the physiological role of this switch will be investigated using cellular and mouse models. The way that cold exposure and hormones turn on this switch and the molecular events afterwards in brown and beige fat will be studied. How dysregulation of this switch contributes to metabolic disorders will also be explored. Therefore, targeting this molecular switch in human may provide new therapies to treat obesity and type II diabetes.