title: Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2.
abstract: Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermentation of "indigestible" prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quantitative PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1-secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes.
authors.affiliation: Cambridge Institute for Medical Research, Wellcome Trust/Medical Research Council Building, Addenbrooke’s Hospital, Cambridge, UK.
authors.forename: Gwen
authors.initials: G
authors.lastname: Tolhurst
authors.forename: Helen
authors.initials: H
authors.lastname: Heffron
authors.forename: Yu Shan
authors.initials: YS
authors.lastname: Lam
authors.forename: Helen E
authors.initials: HE
authors.lastname: Parker
authors.forename: Abdella M
authors.initials: AM
authors.lastname: Habib
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Diakogiannaki
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cameron
authors.forename: Johannes
authors.initials: J
authors.lastname: Grosse
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000494:pharmacology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D005232:Fatty Acids, Volatile; C506481:Ffar2 protein, mouse; C506482:Gpcr41 protein, mouse; D043562:Receptors, G-Protein-Coupled; D052216:Glucagon-Like Peptide 1; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium