Cell Metabolism
Volume 11, Issue 3, 3 March 2010, Pages 183-193
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Article
Loss of TGH/Ces3 in Mice Decreases Blood Lipids, Improves Glucose Tolerance, and Increases Energy Expenditure

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Summary

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.

Highlights

► Triacylglycerol hydrolase participates in adipose and liver lipid metabolism ► Loss of TGH lowers plasma fatty acid and triglyceride levels in mice ► Loss of TGH increases energy expenditure in mice ► Loss of TGH results in improved glucose metabolism and β cell function

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