[PDF][PDF] Loss of TGH/Ces3 in mice decreases blood lipids, improves glucose tolerance, and increases energy expenditure

E Wei, YB Ali, J Lyon, H Wang, R Nelson, VW Dolinsky… - Cell metabolism, 2010 - cell.com
E Wei, YB Ali, J Lyon, H Wang, R Nelson, VW Dolinsky, JRB Dyck, G Mitchell, GS Korbutt
Cell metabolism, 2010cell.com
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 …
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.
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