Brooks, L;
Viardot, A;
Tsakmaki, A;
Stolarczyk, E;
Howard, JK;
Cani, PD;
Everard, A;
... Bewick, GA; + view all
(2017)
Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety.
Molecular Metabolism
, 6
(1)
pp. 48-60.
10.1016/j.molmet.2016.10.011.
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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 characterized and gut hormone concentrations, enteroendocrine cell density measurements were carried out. Intestinal organoids and colonic cultures were utilized 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-suppressing 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.
| Type: | Article |
|---|---|
| Title: | Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.molmet.2016.10.011 |
| Publisher version: | https://doi.org/10.1016/j.molmet.2016.10.011 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Obesity, Diet, Peptide YY, Microbiota, Colon |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10053142 |
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