Effects of clofibrate on ethanol-induced modifications in liver and adipose tissue metabolism: Role of hepatic redox state and hormonal mechanisms

Abstract

Mechanisms by which clofibrate decreases the development of acute alcoholic fatty liver were studied, especially in regard to hepatic redox state and hormonal regulation of carbohydrate and lipid metabolism. A partial inhibition of the ethanol-induced increase in cytosolic NADH/NAD ratio was observed. As a result, in clofibrate-treated rats hepatic α-GP concentration during ethanol oxidation also remained at the same level as in normal control rats. Clofibrate treatment prevented the ethanol-induced increase in the adipose tissue cAMP and plasma FFA concentrations. Hepatic concentrations of CoA-SH, acetyl-CoA and long chain acyl-CoA were markedly increased by clofibrate treatment. Plasma insulin concentration was decreased in clofibrate-treated rats, which also showed an impaired glucose tolerance. The results show that clofibrate is able to restrict the availability of substrates (α-GP and fatty acids) for hepatic triglyceride synthesis in vivo. In addition, it was concluded that the partial inhibition of ethanol-induced fatty liver by clofibrate may result from the enhancement of the oxidation pathway of fatty acid metabolism as suggested by the enormous increase in hepatic content of CoA-SH and its derivatives.