THE EFFECTS OF SHORT-CHAIN FATTY ACIDS AND STARVATION ON THE METABOLISM OF GLUCOSE AND LACTATE BY THE PERFUSED GUINEA PIG HEART

Abstract

Uniformly labelled14C-glucose, when present at a concentration of 5 mM, is oxidized to14CO2by perfused guinea pig hearts at a rate of 10 μmoles per g wet weight per hour. Radioactivity is incorporated into glutamate, glutamine, alanine, aspartate, and heart proteins. During perfusion for 1 hour there is a high rate of incorporation of14C-glucose into glycogen and very little radioactive lactate accumulates. The cardiac glycogen is not increased.The oxidation of14C-glucose to14CO2by perfused hearts is suppressed more than 90% by prolonged starvation or by addition of acetate, butyrate, or pentanoate. The incorporation of radioactivity into glutamate and glutamine is almost completely blocked, while the radioactive labelling in alanine is undiminished. Cardiac glycogen of guinea pigs is increased approximately threefold by a 72-hour fast. Lactate production is increased in hearts of starved animals and by exogenous fatty acids. The short-chain fatty acids mentioned increase the net incorporation of exogenous glucose into cardiac glycogen, and there is apparently less net glycogenolysis in their presence than in their absence. Propionate reduces glucose oxidation to CO2by about 40% and has a much less pronounced effect on incorporation of glucose carbon into glutamate than that of acetate or butyrate. It has little effect on incorporation of exogenous glucose into cardiac glycogen, or on the amount of lactate which accumulates in the perfusing medium.1-14C-Lactate and 2-14C-lactate are rapidly oxidized to14CO2, and radioactivity from 2-14C-lactate is incorporated into glutamate, glutamine, alanine, and aspartate. Starvation, or the presence of acetate, butyrate, or pentanoate, suppresses lactate oxidation and incorporation of its carbon into glutamate and glutamine. The utilization of14C-lactate is diminished by these fatty acids to about the same extent as that of14C-glucose.These results may be explained by an inhibitory effect of acetyl-CoA on pyruvate oxidation by guinea pig hearts.1-14C-Acetate, 1-,4C-propionate, and 1-14C-butyrate are rapidly oxidized to14CO2and the labelled C is incorporated into glutamate, glutamine, and aspartate. Oxidation of acetate is not affected by starvation or by the presence of glucose or of propionate.