Role of ß-arrestin-2 in adipocytes

ß-Arrestins are major regulators of G protein-coupled receptor-mediated signalingprocesses. Their potential roles in regulating adipocyte function in vivo remainunexplored. Here we report the novel finding that mice lacking ß-arrestin-2 (barr2)selectively in adipocytes show significantly reduced adiposity and striking metabolicimprovements when consuming excess calories. We demonstrate that these beneficialmetabolic effects are due to enhanced signaling through adipocyte ß3-adrenergicreceptors (ß3-ARs), indicating that barr2 represents a potent negative regulator ofadipocyte ß3-AR activity in vivo. Interestingly, essentially all beneficial metabolic effectscaused by adipocyte barr2 deficiency are absent in adipocyte barr2-PRDM16 double KOmice, indicating that the metabolic improvements caused by the lack of barr2 inadipocytes are mediated by the browning/beiging of white adipose tissue.