Effects of Volatile Fatty Acids on Propionate Metabolism and Gluconeogenesis in Caprine Hepatocytes

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Abstract
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 production was not competitive. Isovalerate had no effect on either [2-14C]propioante incorporation into glucose or 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 genetrate a net synthesis of intracellular oxaloacetate may partition propionate carbons toward gluconeogenic rather than oxidative pathways in goat hepatocytes.