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

First Author  Lian J Year  2012
Journal  Hepatology Volume  56
Issue  6 Pages  2154-62
PubMed ID  22707181 Mgi Jnum  J:299560
Mgi Id  MGI:6501227 Doi  10.1002/hep.25881
Citation  Lian J, et al. (2012) Liver specific inactivation of carboxylesterase 3/triacylglycerol hydrolase decreases blood lipids without causing severe steatosis in mice. Hepatology 56(6):2154-62
abstractText  UNLABELLED: 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.
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