Roles of Short-Chain Fatty Acids and their Receptors in Colonic Motility

Abstract

Short chain fatty acids (SCFAs) are major anions in the large intestine. They are produced by bacterial fermentation of dietary fiber. However, the mechanism by which intraluminal SCFAs are sensed is unknown. Free fatty acids including SCFAs have recently been demonstrated to act as ligands for several G-protein-coupled receptors (GPCRs: FFA1, FFA2, FFA3, GPR84, GPR109A and GPR120). SCFAs are ligands for FFA2 and FFA3. These receptors are proposed to play a variety of physiological and pathophysiological roles in the intestine. In rat and human colons, FFA2 and/or FFA3 are located in mucosal enteroendocrine cells containing peptide YY (PYY) and are related to energy balance. Among SCFAs, propionate and butyrate induce concentration-dependent phasic and tonic contractions in rat colonic circular muscle. These responses are not observed in mucosal free preparations. Thus, FFA2 and FFA3 are important molecular devices for monitoring the chemical composition in the colonic lumen. For the local function of SCFAs, it should be stressed that individual SCFAs have different modes of action on colonic smooth muscles. These different actions may be due to the relative contributions of FFA2 and FFA3 to the control of intestinal muscle activity. FFA2 and FFA3 may also contribute to the whole body energy balance through the release of gastrointestinal hormones related to feeding and satiety control. This review summarizes recent findings about the roles of deorphanized FFA receptors, especially, FFA2 and FFA3 and their contributions to the regulation of colonic motility.