Metabolism of short-chain fatty acids by rat colonic mucosa in vivo

To determine the influence of substrate concentration and substrate interac tions on short-chain fatty acid metabolism in vivo, a surgical procedure wa s established. Rats were surgically operated to cannulate a 5-cm segment of proximal colon, isolate the vasculature, and cannulate the right colic vei n draining this segment. Thus metabolism was restricted to the defined colo nic segment.; The appearance of total C-14 and (CO2)-C-14 in the mesenteric blood stabilized after 30 min of perfusion. Increasing luminal concentrati ons of butyrate from 2 to 40 mmol/l resulted in linear increases in total C -14, but (CO2)-C-14 production from [C-14]butyrate increased as a function of concentration only up to 10 mmol/l and was stable at higher butyrate con centrations. In addition to CO2, 3-hydroxybutyrate and lactate were major m etabolites of acetate and butyrate in vivo. The presence of a mixture of al ternative substrates in the lumen had no influence on the metabolism of but yrate to CO2 but significantly reduced the metabolism of acetate to CO2. Wh en compared with young (4 mo old) animals, transport of butyrate was signif icantly lower for aged (48 mo old) animals, as evidenced by the rate of app earance in blood of total C-14 (P = 0.04) and C-14 in butyrate (P = 0.03), but metabolism was similar, since differences were not significant for C-14 in the major metabolites 3-hydroxybutyrate (P = 0.06) and CO2 (P = 0.17). These results show that important aspects of short-chain fatty acid transpo rt and metabolism are not predicted from data using isolated colonocytes bu t require study using an in vivo model.