The Effects of Starvation and Refeeding on Carbohydrate and Lipid Metabolism in Vivo and in the Perfused Rat Liver

Abstract

The time course of changes in a variety of physiological parameters concerned with carbohydrate and lipid metabolism has been studied both in vivo and in the isolated perfused liver during induction and reversal of starvation ketosis in the rat. The data obtained demonstrate that surprisingly brief periods of starvation and refeeding exert dramatic effects on glucose and fatty acid metabolism in the intact animal and that generally synchronous changes occur in the ketogenic and gluconeogenic capacities of the perfused liver. In agreement with previous findings it was shown that the enhanced conversion of labeled oleate into ketone bodies by livers from fasted rats was associated with a concomitant depression in its incorporation into triglycerides, and that the antiketogenic effect of lactate was accompanied by a diversion of the fatty acid from the β oxidation sequence into the esterification pathway. The key observation, however, was that blockade of long chain fatty acid oxidation by (+)-decanoylcarnitine, an inhibitor of long chain acylcarnitinetransferase, stopped ketone body formation and acutely changed the pattern of metabolism of oleic acid in livers from fasted rats to that exhibited by livers from normal animals, i.e. the fatty acid was now virtually completely esterified. The data are consistent with the view that hepatic fatty acid oxidation and ketogenesis are under strict dietary and hormonal control exerted primarily by regulation of an early step in the oxidative sequence, probably the acylcarnitinetransferase reaction. The possibility is also raised that the effects of lactate and other antiketogenic agents are related to interactions at this site.