M1718 Fructo-Oligosaccharide (FOS) Supplementation Increases Enteroendocrine L Cells Containing GLP-1 and SCFA Receptor GPR43 (Ffa2) in the Large Intestine

Abstract

Background and aim: Glucagon-like peptide-1 (GLP-1) is known as an incretin and a satiety hormone released by enteroendocrine L-cells, and its plasma concentration is reported to increase by dietary non-digestible carbohydrates such as certain dietary fibers and oligosaccharides. However, the triggers and modulators of the GLP-1 release remain unclear. We have previously reported that the L-cells containing peptide YY (PYY) express short-chain fatty acid (SCFA) receptor GPR43 in human and rat colon. PYY is reported to be contained in the same granules together with GLP-1. In the present study, we therefore investigated 1) the coexpression of GLP-1 and GPR43 in human and rat lower intestine, and 2) the effects of a long-term feeding of fructo-oligosaccharide (FOS) supplemented diet on these expressions in rats. Methods: 1) The expression of GLP-1, 5-hydroxytriptamine (5-HT), and GPR43 in the enteroendocrine cells were quantified by immunohistochemistry in the colon and terminal ileum isolated from rat and surgical specimens of humans. 2) Control and FOS-supplemented rats were fed a non-digestible carbohydrate-free and 5% (w/w) FOScontaining diet (16 g/day), respectively. On the 28th day, the rats were killed. The tissue and content weights of cecum, and GLP-1-, 5-HT-, and GPR43-positive cells in the colon, cecum and terminal ileum were measured. Results: Immunohistochemical analysis confirmed that GPR43-positive enteroendocrine cells were GLP-1-containing L-cells, but not 5-HTcontaining enterochromaffin (EC) cells, both in human and rat colon and terminal ileum. Furthermore, compared to control, 4week FOS (5%) supplementation in rats significantly increased cecal tissue weight (but not its content weight) and the densities (cell number/ mm2 mucosa) of both GLP-1and GPR43-containing L-cells in particular the proximal colon. On the other hand, 5-HT-expressing EC cells were not affected by the FOS supplementation. Conclusion: The results showed that FOS supplementation increased the expression of GLP1and GPR43-containing enteroendocrine L-cells in the large intestine, suggesting that the prebiotic effects of FOS, such as improvement of the colonic environment to protect against pathogen and inflammation, is associated with the expression of the SCFA receptor GPR43. Therefore, it is possible that the long-term FOS ingestion contributes to the prevention of obesity and diabetes through PYY/GLP-1 release mediated by SCFA-stimulation of GPR43 in the large intestine.