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

ABSTRACT: ?-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 ?-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 ?3-adrenergic receptors (?3-ARs), indicating that barr2 represents a potent negative regulator of adipocyte ?3-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' ?3-AR agonists that do not promote ?3-AR/barr2 interactions may prove useful for the treatment of obesity and related metabolic disorders.

SUBMITTER: Pydi SP 

PROVIDER: S-EPMC6610117 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature