EFFECTS OF PROPIONATE ON RAT HEPATOCYTE METABOLISM

The aim of the present study was to investigate the effects of propion ate or even-chain fatty acids (butyrate, octanoate, and oleate) on glu cogenic or ketogenic substrate metabolism as well as ureagenesis. Ther efore, rat hepatocytes were incubated in complex media containing near -physiological concentrations of glucose, lactate, alanine, and glutam ine. On hepatocytes from fed rats, propionate impaired lactate metabol ism, whose threshold for net utilization was shifted from 2.5 mM to mo re than 4 mM, whereas even-chain fatty acids presented the opposite ef fect Furthermore, propionate, in contrast to even-chain fatty acids, e ffectively lowered lactate utilization in hepatocytes from starved rat s. Determination of the cell;lar concentration of glycolysis effecters (citrate, fructose 2,6-bisphosphate, and xylulose 5-phosphate) indica tes that this pathway might be accelerated by propionate and depressed by even-chain fatty acids. Cellular pyruvate was markedly increased b y propionate and depressed by even-chain fatty acids. Thus, the sparin g effect of propionate on lactate seems mainly a consequence of sustai ning high pyruvate concentrations in hepatocytes. Ammonia increased la ctate utilization, and propionate partially thwarted the effect of amm onia 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 signifi cantly decreased in the presence of propionate, whatever the fatty aci d precursor (butyrate, octanoate, or oleate) together with beta-hydrox ybutyrate/acetoacetate ratio. Because propionate did not affect oleate utilization, it could switch fatty acids from ketogenesis to other pa thways like reesterification. Finally, propionate exerts important eff ects on cellular metabolism, and it helps to reduce the catabolism of some substrates such as lactate or oleate. (C) Elsevier Science Inc. 1 998.