Beta-Arrestin 1 Suppresses Myogenic Reprogramming Of Brown Fat To Maintain Euglycemia

A better understanding of the signaling pathways regulating adipocyte function is required for the development of new classes of antidiabetic/obesity drugs. We here report that mice lacking beta-arrestin-1 (barr1), a cytoplasmic and nuclear signaling protein, selectively in adipocytes showed greatly impaired glucose tolerance and insulin sensitivity when consuming an obesogenic diet. In contrast, transgenic mice overexpressing bard in adipocytes were protected against the metabolic deficits caused by a high-calorie diet. Barr1 deficiency led to a myogenic reprogramming of brown adipose tissue (BAT), causing elevated plasma myostatin (Mstn) levels, which in turn led to impaired insulin signaling in multiple peripheral tissues. Additional in vivo studies indicated that bard-mediated suppression of Mstn expression by BAT is required for maintaining euglycemia. These findings convincingly identify bard as a critical regulator of BAT function. Strategies aimed at enhancing bard activity in BAT may prove beneficial for the treatment of type 2 diabetes.