Ethanol oxidation by isolated hepatocytes from ethanol-treated and control rats; factors contributing to the metabolic adaptation after chronic ethanol consumption

Abstract

Chronic consumption of ethanol by rats produced a fatty liver and resulted in a pronounced increase in the rate of ethanol oxidation by isolated hepatocytes. Despite the increase in ethanol oxidation, oxygen consumption with several substrates was not enhanced after chronic ethanol treatment. Ouabain, an inhibitor of the (Na + + K + )-ATPase activity, did not abolish the increase in the rate of ethanol oxidation. About 40–50 per cent of the increase in ethanol oxidation persisted after inhibition of alcohol dehydrogenase, mitochondrial oxygen consumption or the malate-aspartate shuttle. The addition of substrates for the malate-aspartate shuttle slightly increased the rate of ethanol oxidation in hepatocytes from control and ethanol-treated animals. The increased rate of ethanol oxidation was not abolished by the uncoupling agent dinitrophenol. which by itself had little effect on ethanol oxidation. In the presence of aspartate or α-glycerophosphate, dinitrophenol augmented the rate of ethanol oxidation; in the presence of glutamate, the rate of ethanol oxidation was doubled by dinitrophenol. However, the higher rate of ethanol oxidation after ethanol consumption was still found in the presence of various combinations of substrate shuttles, with or without dinitrophenol. Pathways independent of alcohol dehydrogenase may contribute, at least in part, to the increase in ethanol oxidation found after chronic ethanol consumption. It is concluded that ethanol oxidation may be enhanced after chronic ethanol consumption without the estabishment of a hypermetabolic state of the liver.