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

Cell Metab. 2010 Mar 3;11(3):183-93. doi: 10.1016/j.cmet.2010.02.005.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins B / blood*
  • Down-Regulation
  • Eating
  • Energy Metabolism / genetics*
  • Fatty Acids / blood*
  • Glucose / metabolism*
  • Glucose Intolerance
  • Insulin / metabolism*
  • Islets of Langerhans / metabolism
  • Lipase / genetics*
  • Lipase / metabolism
  • Lipoproteins, LDL / metabolism
  • Liver / metabolism
  • Mice
  • Mice, Knockout
  • Triglycerides / blood*


  • Apolipoproteins B
  • Fatty Acids
  • Insulin
  • Lipoproteins, LDL
  • Triglycerides
  • Lipase
  • Glucose