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

Cell Rep. 2020 Mar 10;30(10):3424-3433.e4. doi: 10.1016/j.celrep.2020.02.055.


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.

Keywords: FGF21; UCP1; acute brown and brite/beige adipocytes ablation; inducible mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Beige / metabolism*
  • Adipocytes, Brown / metabolism*
  • Animals
  • Energy Metabolism
  • Fibroblast Growth Factors / metabolism
  • Gene Deletion
  • Mice, Inbred C57BL
  • Models, Genetic*
  • Temperature
  • Uncoupling Protein 1 / metabolism


  • Uncoupling Protein 1
  • fibroblast growth factor 21
  • Fibroblast Growth Factors