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

Jihong Lian, Enhui Wei, Shu Pei Wang, Ariel D. Quiroga, Lena Li, Alba Di Pardo, Jelske van der Veen, Simonetta Sipione, Grant A. Mitchell, Richard Lehner

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2154-2162
Number of pages9
JournalHepatology
Volume56
Issue number6
DOIs
Publication statusPublished - Dec 2012

ASJC Scopus subject areas

  • Hepatology

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    Lian, J., Wei, E., Wang, S. P., Quiroga, A. D., Li, L., Pardo, A. D., van der Veen, J., Sipione, S., Mitchell, G. A., & Lehner, R. (2012). Liver specific inactivation of carboxylesterase 3/triacylglycerol hydrolase decreases blood lipids without causing severe steatosis in mice. Hepatology, 56(6), 2154-2162. https://doi.org/10.1002/hep.25881