Effects of propionate on rate hepatocyte metabolism

The aim of the present study was to investigate the effects of propionate of even-chin fatty acids (butyrate octanoate, and oleate) on glucogenic or ketogenic substrate metabolism as well as ureagenesis. Therefore, rat hepatocytes were incubated in complex media containing near-physiological concentrations of glucose, lactate, alanine, and glutamine. On hepatocytes from fed rats, propionate impaired lactate metabolism, whose threshold for net utilization in hepatocytes was shifted from 2.5 mM to more than 4 mM, whereas even-chain fatty acids, effectively lowered lactate utilization in hepatocytes from starved rats. Determination of the cellular concentration of glycolysis effectors (citrate, fructose 2,6-bisphosphate, and xylulose 5-phosphate) indicates that this pathway might be accelerated by propionate and depressed by even-chain fatty acids. Cellular pyruvate was markedly increased by propionate and depressed by even-chain fatty acids. Thus the sparing effect of propionate on lactate seems mainly a consequence of sustaining high pyruvate concentration in hepatocytes. Ammonia increased lactate utilization, and propionated partially thwarted the effect of ammonia on lactate flux. Propionate did not influence alanine utilization, but favored the production of alanine in an amino acid-free medium. Ketogenesis, very active in hepatocytes from starved rats, was significantly decreased in the presence of propionate, whatever the fatty acid precursor (butyrate, octanoate, or oleate) together with beta-hydroxy butyrate/acetoacetate ratio. Because propionate did not affect oleate utilization, it could switch fatty acids from ketogenesis to other pathways like reesterfication. Finally, propionate exerts important effects on cellular metabolism, and it helps to reduce the catabolism of some substrates such as lactate or oleate.