The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents
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BACKGROUND AND OBJECTIVES: 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.
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SCFAs can stimulate the secretion of GLP-1 and PYY through the FFAR2 receptor and, to a lesser extent, the FFAR3 receptor.
“SCFAs can stimulate the secretion of GLP-1 and PYY through the FFAR2 and, to a lesser extent, the FFAR3 receptor (Lin et al., 2012;Psichas et al., 2015;Tolhurst et al., 2012).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Psichas et al., 2015
The Discussion reports that propionate stimulates GLP-1 and PYY release in rodents and that FFA2 deficiency impairs this response. It mentions FFA3 as part of a hypothesis, but does not establish that FFA3 mediates secretion or that its contribution is smaller than FFA2’s. The supplied passages have no page numbers. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGut microbial metabolites, including SCFAs that are generated by the fermentation of dietary fibre, influence the host endocrine system.
“Gut microbial metabolites, including SCFAs that are generated by the fermentation of dietary fibre, influence the host endocrine system.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [41]
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Identifying crop variants with high resistant starch content to maintain healthy glucose homeostasis
Petropoulou, K., Chambers, E. S., Morrison, D. J., Preston, T., Godsland, I. F., Wilde, P., Narbad, A., Parker, R., Salt, L., Morris, V. J., et al. (2016) · Nutrition Bulletin · doi:10.1111/nbu.12240 · Cited by 7 · see citing works
Self-citation
- Authors
- Psichas, A., Sleeth, M. L., Murphy, K. G., Brooks, L., Bewick, G. A., Hanyaloglu, A. C., Ghatei, M. A., Bloom, S. R., & Frost, G.
- Affiliations
- Imperial College London (GB)
- King's College London (GB)
- Corresponding author
- Frost, G
- Venue
- International Journal of Obesity
- Published
- 2014-08-11
- Volume
- 39
- Issue
- 3
- Pages
- 424-429
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- PMC
- PMC4356745
- OpenAlex
- W2067689880
- Cited by
- 886
- References
- 33
- Citations by year
- 2026: 108 · 2025: 118 · 2024: 98 · 2023: 75 · 2022: 87 · 2021: 79 · 2020: 56 · 2019: 61 · 2018: 72 · 2017: 48 · 2016: 46 · 2015: 31 · 2014: 5
- FWCI
- 20.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Journal of Obesity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research (FP7-HEALTH-2009-241592, FP7-HEALTH-2009-241592 EuroCHIP, NF-SI-0513-10080, NF-SI-0507-10337, CDF-2011-04-006)
- Monash University
- Medical Research Council (FP7-HEALTH-2009-241592)
- Biotechnology and Biological Sciences Research Council (BB/I00842X/1, BB/H014039/1, 1527476, BB/E52708X/1, BB/L004259/1, FP7-HEALTH-2009-241592 EuroCHIP, BB/H004971/1, FP7-HEALTH-2009-241592)
- NIHR Imperial Biomedical Research Centre
- FP7 Health (2009-241592 EuroCHIP)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- propionate, short-chain fatty acids, FFAR2, glucagon-like peptide-1, peptide YY, gut hormone secretion, appetite regulation
- MeSH terms
- Animals, Colon, Gastrointestinal Hormones, Mice, Inbred C57BL, Propionates, Rats, Wistar, Peptide YY, Receptors, G-Protein-Coupled, Mice, Rats, Glucagon-Like Peptide 1
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