A Genetic Model to Study the Contribution of Brown and Brite Adipocytes to Metabolism

UCP1-dependent thermogenesis is studied to define new strategies to ameliorate obesity and type 2 diabetes; however, animal models are mostly limited to germline mutations of UCP1, which can effect adaptive changes in UCP1-independent pathways. We develop an inducible mouse model for the sequential ablation of UCP1(+) brown and brite/beige adipocytes in adult mice. We demonstrate that activated brown adipocytes can increase systemic energy expenditure (EE) by 30%, while the contribution of brite/beige UCP1(+) cells is <5%. Notably, UCP1(+) adipocytes do not contribute to circulating FGF21 levels, either at room temperature or after cold exposure. We demonstrate that the FGF21-mediated effects on EE and glucose homeostasis are partially dependent on the presence of UCP1(+) cells, while the effect on weight loss is not. In conclusion, acute UCP1(+) cell deletion may be a useful model to study the impact of brown and brite/beige adipocytes on metabolism.