Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic ( Agpat2 ^−/−) or obese ( ob/ ob) mice

Abstract

Reducing triacylglycerol (TAG) in the liver continues to pose a challenge in states of nonalcoholic hepatic steatosis. Monoacylglycerol O-acyltransferase (MOGAT) enzymes convert monoacylglycerol (MAG) to diacylglycerol, a precursor for TAG synthesis, and are involved in a major pathway of TAG synthesis in selected tissues, such as small intestine. MOGAT1 possesses MGAT activity in in vitro assays, but its physiological function in TAG metabolism is unknown. Recent studies suggest a role for MOGAT1 in hepatic steatosis in lipodystrophic [1-acylglycerol-3-phosphate O-acyltransferase ( Agpat) 2 ^−/−] and obese ( ob/ ob) mice. To test this, we deleted Mogat1 in the Agpat2 ^−/− and ob/ ob genetic background to generate Mogat1 ^−/− ;Agpat2 ^−/− and Mogat1 ^−/− ;ob/ ob double knockout (DKO) mice. Here we report that, despite the absence of Mogat1 in either DKO mouse model, we did not find any decrease in liver TAG by 16 weeks of age. Additionally, there were no measureable changes in plasma glucose (diabetes) and insulin resistance. Our data indicate a minimal role, if any, of MOGAT1 in liver TAG synthesis, and that TAG synthesis in steatosis associated with lipodystrophy and obesity is independent of MOGAT1. Our findings suggest that MOGAT1 likely has an alternative function in vivo.