Loss of TGH/Ces3 in mice decreases blood lipids, improves glucose tolerance, and increases energy expenditure.
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.
Wei
Enhui
E
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Ben Ali
Yassine
Y
Lyon
James
J
Wang
Huajin
H
Nelson
Randy
R
Dolinsky
Vernon W
VW
Dyck
Jason R B
JR
Mitchell
Grant
G
Korbutt
Gregory S
GS
Lehner
Richard
R
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*
D001055:Apolipoproteins B; D005227:Fatty Acids; D007328:Insulin; D008077:Lipoproteins, LDL; D014280:Triglycerides; D008049:Lipase; D005947:Glucose