Liver specific inactivation of carboxylesterase 3/Triacylglycerol hydrolase decreases blood lipids without causing severe steatosis

LIAN, JIHONG; WEI, ENHUI; WANG, SP; QUIROGA, ARIEL DARIO; LI, LENA; DIPARDO, ALBA; VAN DER VEEN, JELSKE; SIPIONE, SIMONETTA; MITCHELL, GRANT; LEHNER, RICHARD

HEPATOLOGY

Wiley

Año: 2012 p. 1 - 10

0171-6123

Carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) participates in hepatic very-lowdensity lipoprotein (VLDL) assembly and in adipose tissue basal lipolysis. Global ablationof Ces3/Tgh expression decreases serum triacylglycerol and nonesterified fatty acid levelsand improves insulin sensitivity. To understand the tissue-specific role of Ces3/TGH inlipid and glucose homeostasis, we have generated mice with a liver-specific deletion ofCes3/Tgh expression (L-TGH KO). Elimination of hepatic Ces3/Tgh expressiondramatically decreased plasma VLDL-triacylglycerol and VLDL-cholesterolconcentrations but only moderately increased liver triacylglycerol levels in mice fedstandard chow diet. Significantly reduced plasma triacylglycerol and cholesterol withouthepatic steatosis were also observed in L-TGH KO mice challenged with Western diet. LTGHKO mice presented with increased plasma ketone bodies and hepatic fatty acidoxidation. Intrahepatic triacylglycerol in L-TGH KO mice was stored in significantlysmaller lipid droplets. Augmented hepatic triacylglycerol levels in chow-fed L-TGH KOmice did not affect glucose tolerance or glucose production from hepatocytes, but impairedinsulin tolerance was observed in female mice. Conclusion: Our data suggest that ablationof hepatic Ces3/Tgh expression decreases plasma lipid levels without causing severe hepaticsteatosis.