title: MGAT2 deficiency and vertical sleeve gastrectomy have independent metabolic effects in the mouse.
abstract: Vertical sleeve gastrectomy (VSG) is currently one of the most effective treatments for obesity. Despite recent developments, the underlying mechanisms that contribute to the metabolic improvements following bariatric surgery remain unresolved. VSG reduces postprandial intestinal triglyceride (TG) production, but whether the effects of VSG on intestinal metabolism are related to metabolic outcomes has yet to be established. The lipid synthesis enzyme acyl CoA:monoacylglycerol acyltransferase-2 (Mogat2; MGAT2) plays a crucial role in the assimilation of dietary fat in the intestine and in regulation of adiposity stores as well. Given the phenotypic similarities between VSG-operated and MGAT2-deficient animals, we reasoned that this enzyme could also have a key role in mediating the metabolic benefits of VSG. However, VSG reduced body weight and fat mass and improved glucose metabolism similarly in whole body MGAT2-deficient (Mogat2(-/-)) mice and wild-type littermates. Furthermore, along with an increase in energy expenditure, surgically naive Mogat2(-/-) mice had altered macronutrient preference, shifting preference away from fat and toward carbohydrates, and increased locomotor activity. Collectively, these data suggest that the beneficial effects of VSG on body weight and glucose metabolism are independent of MGAT2 activity and rather that they are separate from the effects of MGAT2 deficiency. Because MGAT2 inhibitors are proposed as a pharmacotherapeutic option for obesity, our data suggest that, in addition to increasing energy expenditure, shifting macronutrient preference away from fat could be another important mechanism by which these compounds could contribute to weight loss.
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Joram D
authors.identifier: http://orcid.org/0000-0003-0453-2568
authors.initials: JD
authors.lastname: Mul
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio; School of Psychology, University of New South Wales, Sydney, New South Wales, Australia;
authors.forename: Denovan P
authors.initials: DP
authors.lastname: Begg
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
authors.forename: April M
authors.initials: AM
authors.lastname: Haller
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Josh W
authors.initials: JW
authors.lastname: Pressler
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Joyce
authors.initials: J
authors.lastname: Sorrell
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, California; Departments of Medicine, Biochemistry, and Biophysics, University of California, San Francisco, California; and.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Farese
authors.affiliation: North Campus Research Complex, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio; darleens@umich.edu.
authors.forename: Darleen A
authors.initials: DA
authors.lastname: Sandoval
mesh_terms: D000818:Animals; D001823:Body Composition; D001835:Body Weight; D018752:Diet, Fat-Restricted; D004435:Eating; D005518:Food Preferences; D005743:Gastrectomy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency*; D009765:Obesity / Q000235:genetics
chemical_list: D017351:N-Acetylglucosaminyltransferases; C063313:alpha-1,6-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase
keywords: acyl-CoA:monoacylglycerol acyltransferase-2; glucose homeostasis; lipid homeostasis; macronutrient preference; vertical sleeve gastrectomy