Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine

Abstract

Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are the major anions in the large intestinal lumen. They are produced from dietary fiber by bacterial fermentation and are known to have a variety of physiological and pathophysiological effects on the intestine. In the present study, we investigated the expression of the SCFA receptor, GPR43, in the rat distal ileum and colon. Expression of GPR43 was detected by reverse transcriptase/polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. mRNA for GPR43 was detected, by RT-PCR, in extracts of the whole wall and separated mucosa from the ileum and colon and from muscle plus submucosa from the ileum, but not from muscle plus submucosa preparations from the colon. We raised a rabbit antiserum against a synthesized fragment of rat GPR43; this was specific for rat GPR43. GPR43 protein was detected by Western blot analysis in extracts of whole wall and separated mucosa, but not in muscle plus submucosa extracts. By immunohistochemistry, GPR43 immunoreactivity was localized to enteroendocrine cells expressing peptide YY (PYY), whereas 5-hydroxytryptamine (5-HT)-immunoreactive (IR) enteroendocrine cells were not immunoreactive for GPR43. Mast cells of the lamina propria expressing 5-HT were also GPR43-IR. The results of the present study suggest that the PYY-containing enteroendocrine cells and 5-HT-containing mucosal mast cells sense SCFAs via the GPR43 receptor. This is consistent with physiological data showing that SCFAs stimulate the release of PYY and 5-HT from the ileum and colon.

Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2−/−) mice

“…Recently a lot of attention has been focused on short-chain fatty acids (SCFA) in distal gut health [37]. SCFA are substrates for G-protein coupled receptors GPR-41 and GPR-43 and regulate colonic water and bicarbonate secretion and gut motility [38,39]. Fatty acids not only exert nutritional effect on the gut but also are protective for enterocytes, serve as activators of transcription, and constitute precursors of inflammatory mediators [40,41].…”

Do SCFA have a role in appetite regulation?

“…In the colon, molecular investigations of cell lines of both rat and human origin have shown that FFA2 and FFA3 are co-localised with the anorexigenic 'ileal brake' gut hormone peptide YY (PYY) in enteroendocrine L-cells (28)(29)(30) . When administered in vitro to a vascularly infused rat colon lumen, solutions of propionate, butyrate, but not acetate stimulate PYY secretion (31) , with no significant release of the gut hormone glucagon-like protein 1 (GLP-1) (32) .…”

“…In vivo, luminal administration of SCFA solutions to live rats and large white pigs have been shown to significantly increase subsequent blood PYY concentrations (33,34) and reduce upper gastrointestinal motility (33) , an effect reproduced with a PYY infusion (33) . As sensitivity to stimulation in vitro is in the order propionate ‡ butyrate > >acetate for PYY secretion (28)(29)(30) , FFA3 is implicated as the responsible receptor for modulating these effects.…”

“…L-rhamnose was investigated as previously published data suggest propionate production is favoured during L-rhamnose fermentation, both in vitro (73) and in vivo (74) . Propionate is the most potent ligand for the SCFA receptor FFA3 and appears to promote leptin expression (26,27) and the production of PYY (28)(29)(30)(31)(32)(33)(34) as discussed earlier, providing a (59) Consumed daily for 12 weeks either: Chronic two-way parallel Healthy obese (n 51)…”

Fatty Acid Binding Receptors and Their Physiological Role in Type 2 Diabetes

“…The physiological concentrations of SCFAs, after a meal, are typically around 100 mM in the lumen of the non-ruminant mammalian large intestine [39]. In contrast, the plasma concentrations of SCFAs are in lM range.…”