Expression of the peroxisome proliferator-activated receptor gene is decreased in experimental alcoholic liver disease.

Peroxisome proliferator-activated receptor (PPAR) and retinoid x receptor (RXR) play important roles in fatty acid metabolism. The present study examined the regulation of retinoic acid receptor (RAR alpha, beta, and gamma), RXR (alpha, beta, and gamma), PPAR, cytochrome P450 2E1 (CYP2E1), catalase, and beta-actin gene expression in chronic alcoholic liver disease in the rat. The results demonstrated that the expression of genes for RAR and RXR isoforms and catalase were not altered by ethanol in the fatty liver. In contrast, the levels of PPAR and CYP2E1 mRNAs were down- and up-regulated by ethanol in the liver, respectively. The levels of CYP2E1 mRNAs correlated positively with blood alcohol levels (BAL). In addition, ethanol induced expression of beta-actin mRNA was also proportional to the BAL. The level of PPAR mRNA and the content of polyunsaturated fatty acid decreased in ethanol-fed rat livers. Decreased PPAR gene expression in ethanol-fed rats might result from a decrease in the content of polyunsaturated fatty acid in the liver. However, the activities of enzymes involved in hepatic lipid metabolism, including acyl CoA synthetase, acyl CoA oxidase, catalase, and protein kinase C, were not changed by ethanol treatment. The significance of down-regulation of PPAR gene in alcohol liver disease is discussed.