Liver specific inactivation of carboxylesterase 3/triacylglycerol hydrolase decreases blood lipids without causing severe steatosis in mice

Hepatology. 2012 Dec;56(6):2154-62. doi: 10.1002/hep.25881.


Carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) participates in hepatic very low-density lipoprotein (VLDL) assembly and in adipose tissue basal lipolysis. Global ablation of Ces3/Tgh expression decreases serum triacylglycerol (TG) and nonesterified fatty acid levels and improves insulin sensitivity. To understand the tissue-specific role of Ces3/TGH in lipid and glucose homeostasis, we generated mice with a liver-specific deletion of Ces3/Tgh expression (L-TGH knockout [KO]). Elimination of hepatic Ces3/Tgh expression dramatically decreased plasma VLDL TG and VLDL cholesterol concentrations but only moderately increased liver TG levels in mice fed a standard chow diet. Significantly reduced plasma TG and cholesterol without hepatic steatosis were also observed in L-TGH KO mice challenged with a high-fat, high-cholesterol diet. L-TGH KO mice presented with increased plasma ketone bodies and hepatic fatty acid oxidation. Intrahepatic TG in L-TGH KO mice was stored in significantly smaller lipid droplets. Augmented hepatic TG levels in chow-fed L-TGH KO mice did not affect glucose tolerance or glucose production from hepatocytes, but impaired insulin tolerance was observed in female mice.

Conclusion: Our data suggest that ablation of hepatic Ces3/Tgh expression decreases plasma lipid levels without causing severe hepatic steatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol, Dietary / administration & dosage
  • Cholesterol, VLDL / blood*
  • Cholesterol, VLDL / metabolism
  • Dietary Fats / administration & dosage
  • Fatty Acids / metabolism
  • Fatty Liver / metabolism
  • Female
  • Glucose / biosynthesis
  • Glucose Tolerance Test
  • Insulin / metabolism
  • Insulin Resistance
  • Ketone Bodies / blood
  • Lipase / deficiency*
  • Lipase / genetics
  • Lipoproteins, VLDL / blood*
  • Lipoproteins, VLDL / metabolism
  • Liver / enzymology*
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Signal Transduction
  • Triglycerides / blood*
  • Triglycerides / metabolism


  • Cholesterol, Dietary
  • Cholesterol, VLDL
  • Dietary Fats
  • Fatty Acids
  • Insulin
  • Ketone Bodies
  • Lipoproteins, VLDL
  • Triglycerides
  • very low density lipoprotein triglyceride
  • Lipase
  • Glucose