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Hepatic lipid accumulation in apolipoprotein C-I-deficient mice is potentiated by cholesteryl ester transfer protein

Author: Gautier, T. · Tietge, U.J.F. · Boverhof, R. · Perton, F.G. · Le Guern, N. · Masson, D. · Rensen, P.C.N. · Havekes, L.M. · Lagrost, L. · Kuipers, F.
Type:article
Date:2007
Institution: TNO Kwaliteit van Leven
Source:Journal of Lipid Research, 1, 48, 30-40
Identifier: 239797
doi: doi:10.1194/jlr.M600205-JLR200
Keywords: Biology · Biomedical Research · Bile · Cholesterol · Triglycerides · bile acid · cholesterol · cholesterol ester transfer protein · high density lipoprotein · triacylglycerol · very low density lipoprotein · animal model · bile secretion · cholesterol blood level · controlled study · insulin metabolism · lipid metabolism · lipid storage · mouse · nonhuman · stress · Animals · Apolipoprotein C-I · Cholesterol Ester Transfer Proteins · Gallbladder · Lipids · Liver · Mice · Mice, Inbred C57BL · Mice, Knockout · Polymerase Chain Reaction · RNA

Abstract

The impact of apolipoprotein C-I (apoC-I) deficiency on hepatic lipid metabolism was addressed in mice in the presence or the absence of cholesteryl ester transfer protein (CETP). In addition to the expected moderate reduction in plasma cholesterol levels, apoCIKO mice showed significant increases in the hepatic content of cholesteryl esters (+58%) and triglycerides (+118%) and in biliary cholesterol concentration (+35%) as compared with wild-type mice. In the presence of CETP, hepatic alterations resulting from apoC-I deficiency were enforced, with up to 58% and 302% increases in hepatic levels of cholesteryl esters and triglycerides in CETPTg/apoCIKO mice versus CETPTg mice, respectively. Biliary levels of cholesterol, phospholipids, and bile acids were increased by 88, 77, and 20%, respectively, whereas total cholesterol, HDL cholesterol, and triglyceride concentrations in plasma were further reduced in CETPTg/apoCIKO mice versus CETPTg mice. Finally, apoC-I deficiency was not associated with altered VLDL production rate. In line with the previously recognized inhibition of lipoprotein clearance by apoC-I, apoCI deficiency led to decreased plasma lipid concentration, hepatic lipid accumulation, and increased biliary excretion of cholesterol. The effect was even greater when the alternate reverse cholesterol transport pathway via VLDL/LDL was boosted in the presence of CETP. Copyright ©2007 by the American Society for Biochemistry and Molecular Biology, Inc.