The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents
By A. Psichas, M. Sleeth, K. Murphy, Lucy Brooks, G. Bewick, A. Hanyaloglu, M. Ghatei, Stephen R. Bloom, G. Frost. International Journal of Obesity, 2014
779 citations recorded by the source corpus.
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.
Subfields: Endocrine and Autonomic Systems, Endocrinology, Diabetes and Metabolism, Nutrition and Dietetics
View Paper: https://www.semanticscholar.org/paper/c9d29092147b915cec82fdb16fe550916a3670b6
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In Nutrition and Dietetics
Citations in the corpus
- Short chain fatty acids in human gut and metabolic health. (2020, positive): “Several studies in in vitro models of enteroendocrine cell lines have probed this effect of SCFA in gut hormone release, (Psichas et al. , 2014; Tolhurst et al. ).”
- The human gut microbiota: Metabolism and perspective in obesity (2018, background): “The modulation of the gut microbiota with prebiotic (oligofructose) of healthy subjects resulted in increased bacterial fermentation, glucose tolerance, and reduced appetite from increased concentrations of GLP1 and PYY,(74) probably due to a mechanism associated with the production of propionate by”
- Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism (2016, background): “tant initiating event for the gut-hormone derived signal.(55,56)”
- Microbiota in health and diseases (2022, background): “For instance, SCFAs can bind to Free Fatty Acid Receptor FFAR2 or FFAR3 on intestinal L cells, stimulating the release of glucagon-like peptide-1 (GLP-1) and peptide YY, which are known to promote insulin secretion and reduce glucagon.(183) In addition, butyrates can protect the integrity of the int”
- Butyrate: A Double-Edged Sword for Health? (2018, background): “Similarly, PYY is also synthesized and released from endocrine L cells throughout the intestinal tract (96, 97) and is implicated in the regulation of food intake, gut motility, and insulin secretion (98, 99).”
- SCFA: mechanisms and functional importance in the gut (2020, background): “If propionate and acetate are strong stimuli for PYY and GLP-1 secretion in rodents at low concentrations, much higher concentrations are required to induce secretion in human subjects((110,113)).”