Hepatic gene expression and lipid parameters in complement C3-/- mice that do not develop ethanol-induced steatosis

被引:41
作者
Bykov, Igor
Jauhiainen, Matti
Olkkonen, Vesa M.
Saarikoski, Sirkku T.
Ehnholm, Christian
Junnikkala, Sami
Vakeva, Antti
Lindros, Kai O.
Meri, Seppo
机构
[1] Mol Med, Helsinki 00250, Finland
[2] Univ Helsinki, Dept Bacteriol & Immunol, Helsinki, Finland
[3] Univ Helsinki, Cent Hosp, Helsinki, Finland
基金
芬兰科学院;
关键词
C3; deficiency; alternative complement pathway; alcoholic liver steatosis; lipoproteins; hepatic gene expression; mouse microarray;
D O I
10.1016/j.jhep.2006.11.020
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: Fatty infiltration initiates alcohol-induced liver changes and complement component C3 affects lipid metabolism. We recently observed that ethanol-induced steatosis seen in normal (C3(+/+)) mice was absent in livers of C3-deficient (C3(-/-)) mice. To understand the underlying molecular mechanisms we analyzed lipid parameters and liver gene expression profiles in these mice. Methods: A Western-type high-fat diet with ethanol or carbohydrates (control) was fed for 6 weeks to C3(+/+) and C3(-/-) mice. Serum and liver lipid parameters were analyzed and liver mRNA expression patterns studied by micro-array analysis and RT-PCR. Results:ln both genotypes ethanol markedly reduced serum cholesterol, apolipoprotein A-I, phospholipid transfer protein activity and hepatic mRNA levels of fatty acid-binding proteins and fatty acid P-oxidation enzymes. In contrast, exclusively in C3(-/-) mice, ethanol treatment increased serum and liver adiponectin levels but down-regulated transcripts of lipogenic enzymes, adiponectin receptor 2 and adipose differentiation-related protein and up-regulated phospholipase D1. Conclusions: We propose that these ethanol-induced alterations observed exclusively in C3(-/-) mice contribute to protection against fatty infiltration and subsequent inflammatory processes in the liver of these mice. The results suggest important cross-talk between complement factor C3 and lipid regulators in ethanol-induced steatosis. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:907 / 914
页数:8
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