A novel batokine Breg controls adipose thermogenesis and glucose homeostasis

Abstract

Batokines selectively expressed in brown and beige adipocytes remain to be identified and their potential signaling role in adipose thermogenesis are largely unknown. Here we identified a batokine we named as Breg acting as a key regulator for adipose thermogenesis and glucose homeostasis. Breg expression is adipose-specific and highly brown fat-enriched, and its secretion is stimulated by {beta}3-adrenergic activation. Gain-of-functional studies collectively showed that secreted Breg promotes adipose thermogenesis, lowers glucose level, and protects against obesity. Adipose-specific Breg knockout mice are defective in white fat browning, and are susceptible to high fat diet-induced obesity and hyperglycemia, demonstrating the physiological importance of this batokine in energy metabolism. Mechanistically, Breg binds to a putative receptor on adipocyte surface and activates protein kinase A independently of {beta}-adrenergic signaling. These results establish Breg as a major upstream signaling component in thermogenesis and offer a potential avenue for the treatment of obesity and diabetes.