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Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety

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Title: Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety
Authors: Brooks, L
Viardot, A
Tsakmaki, A
Stolarczyk, E
Howard, JK
Cani, PD
Everard, A
Sleeth, ML
Psichas, A
Anastasovskaj, J
Bell, JD
Bell-Anderson, K
Mackay, CR
Ghatei, MA
Bloom, SR
Frost, G
Bewick, GA
Item Type: Journal Article
Abstract: Objective Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1. Methods Wild-type or Ffar2-/-mice were fed an inulin supplemented or control diet. Mice were metabolically characterised and gut hormone concentrations, enteroendocrine cell density measurements were carried out. Intestinal organoids and colonic cultures were utilised to substantiate the in vivo findings. Results We provide new mechanistic insight into how fermentable carbohydrate regulates metabolism. Using mice that lack FFAR2, we demonstrate that the fermentable carbohydrate, inulin, acts via this receptor to drive an 87% increase in the density of cells that produce the appetite-supressing hormone peptide YY (PYY), reduce food intake and prevent diet-induced obesity. Conclusion Our results demonstrate that FFAR2 is predominantly involved in regulating the effects of fermentable carbohydrate on metabolism and does so, in part, by enhancing PYY cell density and release. This highlights the potential for targeting enteroendocrine cell differentiation to treat obesity.
Issue Date: 4-Nov-2016
Date of Acceptance: 28-Oct-2016
URI: http://hdl.handle.net/10044/1/42201
DOI: https://dx.doi.org/10.1016/j.molmet.2016.10.011
ISSN: 2212-8778
Publisher: Elsevier
Start Page: 48
End Page: 60
Journal / Book Title: Molecular Metabolism
Volume: 6
Copyright Statement: © 2016 Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Keywords: Colon
Diet
Microbiota
Obesity
Peptide YY
Publication Status: Published
Appears in Collections:Division of Surgery
Clinical Sciences
Molecular Sciences
Department of Medicine
Faculty of Medicine



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