Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pH-dependent and carrier mediated transport mechanism

The short-chain fatty acids, acetate, propionate, and butyrate, are the mos t abundant organic anions in the human colon. SCFA play a pivotal role in m aintaining homeostasis in the colon. Particularly butyrate induces cell dif ferentiation and regulates growth and proliferation of colonic mucosal epit helial cells, whereas it reduces the growth rate of colorectal cancer cell. Previous studies by several groups, including our own, using isolated memb rane vesicles have demonstrated that the uptake of butyrate is at least in part mediated by a non-electrogenic SCFA-/HCO3- antiporter. The pur pose of the present study was to determine (1) whether Caco-2 cells could serve as an experimental model to assess the mechanisms of SCFA transport, and (2) whether monocarboxlate transporters could play a role in SCFA transport in these cells. Caco-2 cells were found to transport C-14-butyrate in a concen tration and time dependent manner. The uptake was sodium independent, but w as stimulated by lowering extracellular pH. The uptake of 500 mu M butyrate was reduced by 49.6% +/- 3.3% in the presence of propionate and by 57.2% /- 4.8% in the presence of 10 mM L-lactate. The addition of 1 mM alpha-cyan o-4-hydroxycinnamate and phloretin, both known to be potent inhibitors of M CT1. decreased the uptake of 500 mu M C-14-butyrate by 59.4% +/- 4.1% and 4 8.9% +/- 3.3%, respectively, whereas similar concentrations of DIDS did not have any effect. These data suggest that the uptake of butyrate in Caco-2 cells occurs via a carrier mediated transport system specific for monocarbo xylic acids, which is in accordance with characteristics of the MCT 1.