Adipocyte β-arrestin-2 is essential for maintaining whole body glucose and energy homeostasis.

Published online

Journal Article

β-Arrestins are major regulators of G protein-coupled receptor-mediated signaling processes. Their potential roles in regulating adipocyte function in vivo remain unexplored. Here we report the novel finding that mice lacking β-arrestin-2 (barr2) selectively in adipocytes show significantly reduced adiposity and striking metabolic improvements when consuming excess calories. We demonstrate that these beneficial metabolic effects are due to enhanced signaling through adipocyte β3-adrenergic receptors (β3-ARs), indicating that barr2 represents a potent negative regulator of adipocyte β3-AR activity in vivo. Interestingly, essentially all beneficial metabolic effects caused by adipocyte barr2 deficiency are absent in adipocyte barr2-PRDM16 double KO mice, indicating that the metabolic improvements caused by the lack of barr2 in adipocytes are mediated by the browning/beiging of white adipose tissue. Our data support the novel concept that 'G protein-biased' β3-AR agonists that do not promote β3-AR/barr2 interactions may prove useful for the treatment of obesity and related metabolic disorders.

Full Text

Duke Authors

Cited Authors

  • Pydi, SP; Jain, S; Tung, W; Cui, Y; Zhu, L; Sakamoto, W; Jain, S; Abel, BS; Skarulis, MC; Liu, J; Huynh, T; Pacak, K; Caron, MG; Gavrilova, O; Finkel, T; Wess, J

Published Date

  • July 3, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 2936 -

PubMed ID

  • 31270323

Pubmed Central ID

  • 31270323

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-11003-4


  • eng

Conference Location

  • England