Beta-Arrestin-1 Suppresses Myogenic Reprogramming of Brown Fat to Maintain Euglycemia

Beta-Arrestin-1 and -2 (barr1 and barr2, respectively) are intracellular signaling proteins that regulate many important metabolic functions. We here report the novel finding thatmice lacking barr1 selectively in adipocytes (adipo-barr1-KO mice) showed greatly impaired glucose tolerance and insulin sensitivity when consuming an obesogenic diet. In contrast, transgenic mice that overexpressed barr1 in adipocytes (adipo-barr1-OE mice) were protected against the metabolic deficits caused by a high-calorie diet. Surprisingly, the lack of barr1 in adipo-barr1-KO mice led to increased myostatin (Mstn) expression in brown adipose tissue (BAT), resulting in elevated plasma myostatin levels. On the other hand, adipo-barr1-OE mice showed decreased plasma Mstn levels. Additional in vivo studies indicated that barr1-mediated inhibition of Mstn expression by BAT is required for maintaining euglycemia. Our data suggest that strategies aimed at enhancing barr1 expression or activity in BAT may prove beneficial for the treatment of type 2 diabetes.