Title
Hepatic lipid accumulation in apolipoprotein C-I-deficient mice is potentiated by cholesteryl ester transfer protein
Author
TNO Kwaliteit van Leven
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.
Publication year
2007
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.
Subject
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
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DOI
https://doi.org/10.1194/jlr.m600205-jlr200
TNO identifier
239797
ISSN
0022-2275
Source
Journal of Lipid Research, 48 (48), 30-40
Document type
article