title: The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents.
abstract: OBJECTIVE
  The gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) acutely suppress appetite. The short chain fatty acid (SCFA) receptor, free fatty acid receptor 2 (FFA2) is present on colonic enteroendocrine L cells, and a role has been suggested for SCFAs in appetite regulation. Here, we characterise the in vitro and in vivo effects of colonic propionate on PYY and GLP-1 release in rodents, and investigate the role of FFA2 in mediating these effects using FFA2 knockout mice.
  
  
  METHODS
  We used Wistar rats, C57BL6 mice and free fatty acid receptor 2 knockout (FFA(-/-)) mice on a C57BL6 background to explore the impact of the SCFA propionate on PYY and GLP-1 release. Isolated colonic crypt cultures were used to assess the effects of propionate on gut hormone release in vitro. We subsequently developed an in vivo technique to assess gut hormone release into the portal vein following colonic infusion of propionate.
  
  
  RESULTS
  Propionate stimulated the secretion of both PYY and GLP-1 from wild-type primary murine colonic crypt cultures. This effect was significantly attenuated in cultures from FFA2(-/-) mice. Intra-colonic infusion of propionate elevated PYY and GLP-1 levels in jugular vein plasma in rats and in portal vein plasma in both rats and mice. However, propionate did not significantly stimulate gut hormone release in FFA2(-/-) mice.
  
  
  CONCLUSIONS
  Intra-colonic administration of propionate stimulates the concurrent release of both GLP-1 and PYY in rats and mice. These data demonstrate that FFA2 deficiency impairs SCFA-induced gut hormone secretion both in vitro and in vivo.
authors.affiliation: Nutrition and Dietetic Research Group, Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Psichas
authors.affiliation: Nutrition and Dietetic Research Group, Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
authors.forename: M L
authors.initials: ML
authors.lastname: Sleeth
authors.affiliation: Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
authors.forename: K G
authors.initials: KG
authors.lastname: Murphy
authors.affiliation: Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Brooks
authors.affiliation: 1] Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK [2] Division of Diabetes & Nutritional Sciences, Kings College London, Yeovil, UK.
authors.forename: G A
authors.initials: GA
authors.lastname: Bewick
authors.affiliation: Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College, London, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Hanyaloglu
authors.affiliation: Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.affiliation: Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.affiliation: Nutrition and Dietetic Research Group, Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Frost
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019894:Peptide YY / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism*
chemical_list: C506481:Ffar2 protein, mouse; D005768:Gastrointestinal Hormones; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1
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