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Predominant role of sterol response element binding proteins ( SREBP) lipogenic pathways in hepatic steatosis in the murine intragastric ethanol feeding model.
BACKGROUND/AIMS: Alcohol-induced fatty liver is associated with induction of sterol response element binding proteins (SREBPs), transcription factors which regulate expression of genes of lipid synthesis. The contribution of SREBP-1c to alcohol-induced fatty liver and injury was studied. METHODS: Wild type and SREBP1c null mice were fed alcohol or control diet by intragastric infusion for 4 weeks. H&E and TUNEL staining, real-time PCR, RT-PCR, and immunoblotting were applied to analyze alcohol-induced liver injury. RESULTS: ALT, plasma homocysteine, liver cholesterol, and TUNEL positive hepatocytes were increased in alcohol-fed mice as compared to control in both genotypes. Liver triglycerides were increased 4-fold in alcohol-fed wild type mice (87.2+/-7.5 vs. control 22.3+/-3.1mg/g liver) but 1.8-fold in alcohol-fed null mice (27.9+/-4 vs. control 14.5+/-3.8mg/g liver). SREBP-2 and HMG CoA reductase were higher in the null than in wild type. Betaine feeding prevented partially the alcohol-induced changes of hepatic lipids and injury in both genotypes. mRNA of Insig-1 was reduced in both genotypes fed alcohol. No change was detected for the SREBP cleavage-activating protein ( Scap) or S1P in either genotype fed alcohol. CONCLUSIONS: The predominant mechanism of hepatic triglyceride accumulation in the intragastric alcohol fed mouse requires the participation of SREBP-1c. SREBP-2 regulated cholesterol accumulation still occurs.[1]References
- Predominant role of sterol response element binding proteins (SREBP) lipogenic pathways in hepatic steatosis in the murine intragastric ethanol feeding model. Ji, C., Chan, C., Kaplowitz, N. J. Hepatol. (2006)
