Metabolic interactions of fructose and ethanol in perfused liver of normal and thyroxine-treated rats

Combined effects of thyroxine treatment and fructose on the rate of ethanol oxidation, the hepatic redox state and the hepatic oxygen consumption were studied in perfused rat liver. Neither thyroxine treatment nor fructose was found to influence the rate of ethanol elimination by the liver. An ethanol-induced increase in lactate/pyruvate concentration ratio in the perfusion medium was augmented by the simultaneous addition of fructose. Thyroxine treatment markedly inhibited this redox change. In perfused livers of thyroxine-treated rats, fructose and glucose were utilized significantly more rapidly than in normal livers. In both kinds of liver, fructose was metabolized about three times as fast as glucose. Lactate and pyruvate production from fructose was ten times that of glucose. Ethanol had no effect on the rate of fructose or glucose elimination in either group of rats. The glucose production from fructose was greater in normal rat livers than in thyroxine-treated ones and was inhibited by ethanol in normal livers. In perfused livers of normal rats, fructose had a biphasic effect on the respiration. During the first 2 min after the addition of fructose, a stimulation of respiration occurred. The oxygen consumption was then inhibited for 8 to 10 min. In normal rats, after an injection of fructose, the hepatic adenosine triphosphate (ATP) and inorganic phosphate (P i) concentrations diminished coincidently with the respiratory inhibition observed in the perfusions. In perfused livers of hyperthyroid rats, fructose only stimulated the oxygen consumption, but in contrast to normal livers, no inhibition was observed. Hepatic ATP and P i concentrations in these rats were decreased by fructose but not as much as in normal livers. The fructose-induced changes in hepatic oxygen consumption and ATP and P i content are interpreted as an example of mutual control between glycolysis and oxidative metabolism. The mechanism of this phenomenon and its control by thyroid hormones are discussed.