Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice
- College of Pharmacy, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-742 (Korea, Republic of)
- Seoul National University Biomedical Informatics, Seoul National University, Seoul 110-799 (Korea, Republic of)
- College of Medicine, Hanyang University, Seoul133-791 (Korea, Republic of)
- College of Veterinary Medicine, Seoul National University, Seoul 151-742 (Korea, Republic of)
- College of Medicine, Ewha Womans University, Seoul 158-710 (Korea, Republic of)
- College of Veterinary Medicine, Kangwon National University, Chuncheon 200-791 (Korea, Republic of)
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.
- OSTI ID:
- 21077800
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 223, Issue 3; Other Information: DOI: 10.1016/j.taap.2007.06.018; PII: S0041-008X(07)00276-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Honokiol reverses alcoholic fatty liver by inhibiting the maturation of sterol regulatory element binding protein-1c and the expression of its downstream lipogenesis genes
HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPAR{gamma}