META060 activates omega‐3 fatty acid receptor GPR120, reduces weight gain, and increases insulin sensitivity in high‐fat diet fed mice

Abstract

Long chain ω‐3 fatty acids exert anti‐inflammatory and insulin sensitizing effects through the activation of G protein‐coupled receptor 120 (GPR120). GPR120 is expressed in macrophages, intestinal L cells and adipocytes. Activation of GPR120 has been reported to reduce TAB1/TAK1 activation and to inhibit NF‐κB signaling pathway in macrophages. GPR120, through regulation of GLP‐1, plays a major role in glucose homeostasis and insulin sensitivity and may be a novel target for the treatment of type 2 diabetes. Previously, we reported that META060, a modified hop extract, improved arthritic symptoms in a mouse model of collagen induced arthritis. To investigate the effects of META060 on inflammation associated obesity, we examined the activity of META060 at GPR120 in vitro, and the effects of META060 in endocrine cell models. In this study, we identified that META060 activated GPR120 and inhibited inflammation. Moreover, META060 stimulated secretion of GLP‐1 in human intestinal L cells (NCI‐H716) and lipogenesis in adipocytes (3T3‐L1). META060 also was evaluated in a mouse model of high fat diet (HFD) induced obesity and diabetes. Mice supplemented for 14 weeks with META060 (100 mg/kg body weight) exhibited significantly less HFD induced weight gain, reduced fat accumulation in various organs, and improved insulin sensitivity. These data indicate that META060, a novel natural agonist for GPR120, acts as an anti‐inflammatory and improves insulin sensitivity in mice, and may have clinical application for type 2 diabetes. Supported by Metagenics Inc.