AGI July 40/1

Fitch, Mark D., and Sharon E. Fleming. Metabolism of short-chain fatty acids by rat colonic mucosa in vivo. Am. J. Physiol. 277 (Gastrointest. Liver Physiol. 40): G31–G40, 1999.—To determine the influence of substrate concentration and substrate interactions on short-chain fatty acid metabolism in vivo, a surgical procedure was established. Rats were surgically operated to cannulate a 5-cm segment of proximal colon, isolate the vasculature, and cannulate the right colic vein draining this segment. Thus metabolism was restricted to the defined colonic segment. The appearance of total 14C and CO2 in the mesenteric blood stabilized after 30 min of perfusion. Increasing luminal concentrations of butyrate from 2 to 40 mmol/l resulted in linear increases in total 14C, but CO2 production from [14C]butyrate increased as a function of concentration only up to 10 mmol/l and was stable at higher butyrate concentrations. In addition to CO2, 3-hydroxybutyrate and lactate were major metabolites of acetate and butyrate in vivo. The presence of a mixture of alternative substrates in the lumen had no influence on the metabolism of butyrate to CO2 but significantly reduced the metabolism of acetate to CO2. When compared with young (4 mo old) animals, transport of butyrate was significantly lower for aged (48 mo old) animals, as evidenced by the rate of appearance in blood of total 14C (P 5 0.04) and 14C in butyrate (P 5 0.03), but metabolism was similar, since differences were not significant for 14C in the major metabolites 3-hydroxybutyrate (P 5 0.06) and CO2 (P 5 0.17). These results show that important aspects of short-chain fatty acid transport and metabolism are not predicted from data using isolated colonocytes but require study using an in vivo model.