Seminar Abstract

Seminar date: 23-03-2010

Richard Lehner Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Canada

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. Carboxylesterase3/Triacylglycerol Hydrolase (Ces3/TGH), a lipase residing in the endoplasmic reticulum, mobilizes triacylglycerols stored in lipid droplets (LDs) for the secretion of very-low density lipoproteins. Ablation of Ces3/TGH expression in mice (Tgh-/-) results in decreased plasma triacylglycerol, apolipoprotein B and fatty acid levels. 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 that TGH represents an ideal therapeutic target for lowering blood lipid levels.