Propionate modulation of ruminal ketogenesis.

The ruminal epithelium is the primary source, through the metabolism of butyrate, of circulating ketone bodies in fed ruminants. Volatile fatty acid metabolism was investigated in short-term (2-h) incubations of isolated sheep ruminal epithelial cells. Ruminal epithelial cells were isolated from ruminal papillae via serial tryptic digestion. Cells were incubated in the presence of various combinations of butyrate (0, .5, 1, 5, 10, or 25 mM), propionate (0, .1, .5, 1, 5, 10, 25, 50, or 100 mM), acetate (0, .5, 1, 5, 25, 50, or 100 mM), and succinate (0, 5, 15, 50 mM) to evaluate the effects of these substrates on butyrate metabolism. Variables measured included beta-hydroxybutyrate (beta-HBA) and acetoacetate (AcAc) production from butyrate, [14C]butyrate oxidation to 14CO2, and lactate and pyruvate formation from propionate and succinate. Butyrate oxidation to CO2, beta-HBA and total ketones produced (nanomoles of butyrate metabolized per 10(6) cells per minute) were linear over the 2-h incubation period (y = .805X + 2.24, r2 = .78; y = 1.02X - 9.1, r2 = .72; and y = 2.238X - 11.76, r2 = .65, respectively). Acetate inhibited beta-HBA formation from butyrate (P < .05) when present at concentrations greater than 5 mM, although a dose-dependence was not consistently exhibited. However, butyrate oxidation to beta-HBA was stimulated (P < .05) by propionate while acetoacetate production declined (P < .05), resulting in no net change in ketone body production (P > .05). A concomitant increase in lactate and pyruvate production was noted with increasing concentrations of propionate. Succinate addition also increased lactate production by the ruminal epithelial cells. In contrast to propionate, succinate addition resulted in a decrease in beta-HBA formation from butyrate (P < .05). Butyrate metabolism by isolated ruminal epithelial cells is influenced by other VFA produced in the rumen, and propionate-induced stimulation of beta-HBA from butyrate does not seem to be mediated via succinate but rather is a result of a shift in the mitochondrial NADH/NAD status.