Effects of volatile fatty acids on propionate metabolism and gluconeogenesis in caprine hepatocytes

Isolated caprine hepatocytes were incubated with fatty acids of various chain lengths. Short-chain fatty acids effects on rates of gluconeogenesis and oxidation from [2-14C] propionate were determined. Additions of glucose (2.5 mM) had no effect on hepatic [2-14C]-propionate metabolism in the presence and absence of amino acids. A complete mixture of amino acids increased label incorporation from [2-14C] propionate into [14C] glucose by 22%. Butyrate inhibited [2-14C] propionate metabolism and increased the apparent Michaelis constant for [2-14C] propionate incorporation into [14C] glucose from 2.4 +/- 1.5 to 5.6 +/- .9 mM. Butyrate's effects on propionate were similar in the presence and absence of L-carnitine (1 mM). Isobutyrate, 2-methylbutyrate, and valerate (1.25 mM) had no effect on [14C] glucose production but decreased 14CO2 production to 57, 61, and 54% of the control [2-14C] propionate (1.25 mM). This inhibition on 14CO2 was not competitive. Isovalerate had no effect on either [2-14C] propionate incorporation into glucose of CO2. An increase in ratio of [14C] glucose to 14CO2 from [2-14C]-propionate demonstrated that short-chain fatty acids other than butyrate do not inhibit gluconeogenesis from propionate. In addition, fatty acids that generate a net synthesis of intracellular oxaloacetate may partition propionate carbons toward gluconeogenic rather than oxidative pathways in goat hepatocytes