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Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice

Title
Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice
Authors
Yin H.-Q.Kim M.Kim J.-H.Kong G.Kang K.-S.Kim H.-L.Yoon B.-I.Lee M.-O.Lee B.-H.
Ewha Authors
김형래
SCOPUS Author ID
김형래scopus
Issue Date
2007
Journal Title
Toxicology and Applied Pharmacology
ISSN
0041-008XJCR Link
Citation
vol. 223, no. 3, pp. 225 - 233
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Ethanol induces cumulative liver damage including steatosis, steatohepatitis and cirrhosis. The aim of this study is to investigate the global intrahepatic gene expression profile in the mouse liver treated with ethanol. A single oral dose of 0.5 or 5 g/kg ethanol was administered to male ICR mice, and liver samples were obtained after 6, 24 and 72 h. Histopathological evaluation showed typical fatty livers in the high-dose group at 24 h. Microarray analysis identified 28 genes as being ethanol responsive (two-way ANOVA; p < 0.05), after adjustment by the Benjamini-Hochberg multiple testing correction; these genes displayed ≥ 2-fold induction or repression. The expression of genes that are known to be involved in fatty acid synthesis was examined. The transcript for lipogenic transcription factor, sterol regulatory element (SRE)-binding factor 1 (Srebf1), was upregulated by acute ethanol exposure. Of the genes known to contain SRE or SRE-like sequences and to be regulated by SRE-binding protein 1 (SREBP1), those encoding malic enzyme (Mod1), ATP-citrate lyase (Acly), fatty acid synthase (Fasn) and stearyl-CoA desaturase (Scd1) were induced by ethanol. Quantitative real-time PCR confirmed the changes in the expression levels of the selected genes. The change in the Srebf1 mRNA level correlates well with that of the SREBP1 protein expression as well as its binding to the promoters of the target genes. The present study identifies differentially expressed genes that can be applied to the biomarkers for alcohol-binge-induced fatty liver. These results support the hypothesis by which ethanol-induced steatosis in mice is mediated by the fatty acid synthetic pathway regulated by SREBP1. © 2007 Elsevier Inc. All rights reserved.
DOI
10.1016/j.taap.2007.06.018
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의학전문대학원 > 의학과 > Journal papers
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