Hepatic gene expression and lipid parameters in complement C3-/- mice that do not develop ethanol-induced steatosis
Hepatic gene expression and lipid parameters in complement C3-/- mice that do not develop ethanol-induced steatosis
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DOI：
10.1016/j.jhep.2006.11.020
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发表时间：
2007-05-01
影响因子：
25.7
通讯作者：
Meri, Seppo
中科院分区：
文献类型：
--
作者：
Bykov, Igor;Jauhiainen, Matti;Meri, Seppo
背景/目的：脂肪浸润引发酒精诱导的肝脏变化，补体成分C3影响脂质代谢。我们最近观察到在正常（C3（+/+））小鼠中观察到的乙醇诱导的脂肪变性在C3缺陷（C3（-/-））小鼠的肝脏中不存在。为了了解潜在的分子机制，我们分析了脂质参数和肝脏基因表达谱在these mouse.Methods：西方型高脂肪饮食与乙醇或碳水化合物（对照）喂养6周C3（+/+）和C3（-/-）小鼠。分析血清和肝脏脂质参数，并通过微阵列分析和RT-PCR研究肝脏mRNA表达模式。结果：在两种基因型中，乙醇均显着降低血清胆固醇、载脂蛋白A-I、磷脂转移蛋白活性以及脂肪酸结合蛋白和脂肪酸P-氧化酶的肝脏mRNA水平。相反，仅在C3（-/-）小鼠中，乙醇处理增加血清和肝脏脂联素水平，但下调脂肪生成酶、脂联素受体2和脂肪分化相关蛋白的转录，上调磷脂酶D1。我们认为，这些乙醇诱导的变化只在C3（-/-）小鼠有助于防止这些小鼠肝脏中的脂肪浸润和随后的炎症过程。结果表明，在乙醇诱导的脂肪变性中，补体因子C3和脂质调节剂之间存在重要的相互作用。(C)2007年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
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.