title: Loss of TGH/Ces3 in mice decreases blood lipids, improves glucose tolerance, and increases energy expenditure.
abstract: Excessive accumulation of triacylglycerol in peripheral tissues is tightly associated with obesity and has been identified as an independent risk factor for insulin resistance, type 2 diabetes, and cardiovascular complications. Here we show that ablation of carboxylesterase 3 (Ces3)/triacylglycerol hydrolase (TGH) expression in mice (Tgh(-/-)) results in decreased plasma triacylglycerol, apolipoprotein B, and fatty acid levels in both fasted and fed states. Despite the attenuation of very low-density lipoprotein secretion, TGH deficiency does not increase hepatic triacylglycerol levels. Tgh(-/-) mice exhibit increased food intake, respiratory quotient, and energy expenditure without change in body weight. These metabolic changes are accompanied by improved insulin sensitivity and glucose tolerance. Tgh(-/-) mice have smaller sized pancreatic islets but maintain normal glucose-stimulated insulin secretion. These studies demonstrate the potential of TGH as a therapeutic target for lowering blood lipid levels.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Canada.
authors.forename: Enhui
authors.initials: E
authors.lastname: Wei
authors.forename: Yassine
authors.initials: Y
authors.lastname: Ben Ali
authors.forename: James
authors.initials: J
authors.lastname: Lyon
authors.forename: Huajin
authors.initials: H
authors.lastname: Wang
authors.forename: Randy
authors.initials: R
authors.lastname: Nelson
authors.forename: Vernon W
authors.initials: VW
authors.lastname: Dolinsky
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
authors.forename: Grant
authors.initials: G
authors.lastname: Mitchell
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Korbutt
authors.forename: Richard
authors.initials: R
authors.lastname: Lehner
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000097:blood*; D015536:Down-Regulation; D004435:Eating; D004734:Energy Metabolism / Q000235:genetics*; D005227:Fatty Acids / Q000097:blood*; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D014280:Triglycerides / Q000097:blood*
chemical_list: D001055:Apolipoproteins B; D005227:Fatty Acids; D007328:Insulin; D008077:Lipoproteins, LDL; D014280:Triglycerides; D008049:Lipase; D005947:Glucose