The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
GPR41/FFAR3 and GPR43/FFAR2 as Cosensors for Short-Chain Fatty Acids in Enteroendocrine Cells vs FFAR3 in Enteric Neurons and FFAR2 in Enteric Leukocytes
Abstract
The expression of short-chain fatty acid receptors GPR41/FFAR3 and GPR43/ free fatty acid receptor 2 (FFAR2) was studied in the gastrointestinal tract of transgenic monomeric red fluorescent protein (mRFP) reporter mice. In the stomach free fatty acid receptor 3 (FFAR3)-mRFP was expressed in a subpopulation of ghrelin and gastrin cells. In contrast, strong expression of FFAR3-mRFP was observed in all cholecystokinin, glucose-dependent insulinotropic peptide (GIP), and secretin cells of the proximal small intestine and in all glucagon-like peptide-1 (GLP-1), peptide YY, and neurotensin cells of the distal small intestine. Throughout the colon and rectum, FFAR3-mRFP was strongly expressed in the large population of peptide YY and GLP-1 cells and in the neurotensin cells of the proximal colon. A gradient of expression of FFAR3-mRFP was observed in the somatostatin cells from less than 5% in the stomach to more than 95% in the rectum. Substance P-containing enterochromaffin cells displayed a similar gradient of FFAR3-mRFP expression throughout the small intestine. Surprisingly, FFAR3-mRFP was also expressed in the neuronal cells of the submucosal and myenteric ganglia. Quantitative PCR analysis of fluorescence-activated cell sorting (FACS) purified FFAR3-mRFP positive cells confirmed the coexpression with the various peptide hormones as well as key neuronal marker proteins. The FFAR2-mRFP reporter was strongly expressed in a large population of leukocytes in the lamina propria of in particular the small intestine but surprisingly only weakly in a subpopulation of enteroendocrine cells. Nevertheless, synthetic ligands specific for either FFAR3 or FFAR2 each released GLP-1 from colonic crypt cultures and the FFAR2 agonist mobilized intracellular Ca2+ in FFAR2 positive enteroendocrine cells. It is concluded that FFAR3-mRFP serves as a useful marker for the majority of enteroendocrine cells of the small and large intestine and that FFAR3 and FFAR2 both act as sensors for short-chain fatty acids in enteroendocrine cells, whereas FFAR3 apparently has this role alone in enteric neurons and FFAR2 in enteric leukocytes.
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Cites
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The role of short-chain fatty acids in microbiota–gut–brain communication
Dalile, B., Van Oudenhove, L., Vervliet, B., & Verbeke, K. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0157-3 · Cited by 3,357
Gut microbiome and health: mechanistic insights
de Vos, W. M., Tilg, H., Van Hul, M., & Cani, P. D. (2022) · Gut · doi:10.1136/gutjnl-2021-326789 · Cited by 2,388
Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits
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Metadata
- Authors
- Nøhr, M. K., Pedersen, M. H., Gille, A., Egerod, K. L., Engelstoft, M. S., Husted, A. S., Sichlau, R. M., Grunddal, K. V., Seier Poulsen, S., Han, S., Jones, R. M., Offermanns, S., & Schwartz, T. W.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2013-10-01
- Volume
- 154
- Issue
- 10
- Pages
- 3552-3564
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2046315492
- Cited by
- 578
- References
- 8
- FWCI
- 30.94
- Type
- journal article
- Language
- en
- Open access
- closed
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