title: 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. MonoacylglycerolO-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-phosphateO-acyltransferase (Agpat)2(-/-)] and obese (ob/ob) mice. To test this, we deletedMogat1in theAgpat2(-/-)andob/obgenetic background to generateMogat1(-/-);Agpat2(-/-)andMogat1(-/-);ob/obdouble knockout (DKO) mice. Here we report that, despite the absence ofMogat1in 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.
authors.affiliation: Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 Anil.Agarwal@utsouthwestern.edu.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Agarwal
authors.affiliation: Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Katie
authors.initials: K
authors.lastname: Tunison
authors.affiliation: Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Jasbir S
authors.initials: JS
authors.lastname: Dalal
authors.affiliation: Gladstone Institute of Cardiovascular Disease San Francisco, San Francisco, CA 94158.
authors.forename: Chi-Liang Eric
authors.initials: CL
authors.lastname: Yen
authors.affiliation: Gladstone Institute of Cardiovascular Disease San Francisco, San Francisco, CA 94158.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Farese
authors.affiliation: Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 Division of Gastroenterology and Departments of Molecular Genetics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Horton
authors.affiliation: Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Garg
mesh_terms: D000217:Acyltransferases / Q000172:deficiency* / Q000235:genetics*; D000818:Animals; D005260:Female; D017353:Gene Deletion; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D000217:Acyltransferases; C021802:2-acylglycerol O-acyltransferase
keywords: 1-acylglycerol-3-phosphate O-acyltransferase 2; diabetes; fatty liver; lipodystrophy; monoacylglycerol O-acyltransferase 1; ob/ob