Fatty acids are potent modulators of lactate utilization in isolated hepatocytes from fed rats

This work reports the roles of the concentration of lactate and of fatty acids on lactate uptake by liver cells isolated from fed or 24-h starved rats. Hepatocytes isolated from fed rats released lactate and pyruvate. The addition of lactate shifted the lactate balance from net release to net utilization, with a threshold at approximately 2 mM. Lactate favored its own utilization by 1) increasing the lactate-to-pyruvate ratio (L/P) and 2) inhibiting hepatic glycolysis. The addition of oleate to the cells elicited 1) a net reduction of the release of lactate and pyruvate in basal conditions, 2) a marked decrease in the threshold of lactate utilization, down to values close to 0.5 mM, and 3) an important stimulation of the utilization of lactate, at physiological concentrations of 2-3 mM. These changes in lactate utilization induced by oleate were accompanied by a parallel increase of the L/P. Oleate acted by decreasing the cellular concentrations of pyruvate. Such an effect was mediated by 1) an inhibition of glycolysis and 2) a rise in pyruvate utilization toward glucose. Moreover, it seems that the capacity of various fatty acids to stimulate lactate utilization depends on their rate of oxidation by the liver. In liver cells isolated from 24-h starved rats, in keeping with the activation of gluconeogenesis, lactate was utilized by hepatocytes even at low concentrations. Because of the low glycolysis and of the high utilization of pyruvate in these cells, the presence of oleate only induced a moderate increase of lactate utilization (+32%).(ABSTRACT TRUNCATED AT 250 WORDS)