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Mol Metab. 2016 Nov 4;6(1):48-60. doi: 10.1016/j.molmet.2016.10.011. eCollection 2017 Jan.

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

Author information

1
Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, W12 0NN, UK.
2
Diabetes & Metabolism Division, Garvan Institute of Medical Research, Sydney-Darlinghurst, NSW, 2010, Australia.
3
Division of Diabetes and Nutritional Sciences, King's College London, London, SE1 9RT, UK.
4
Louvain Drug Research Institute, Metabolism and Nutrition Research Group, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Université catholique de Louvain, B-1200, Brussels, Belgium.
5
Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London, W12 0NN, UK.
6
School of Molecular Bioscience, University of Sydney, Sydney, NSW, 2006, Australia.
7
Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia; Department of Immunology, Monash University, Clayton, VIC, 3800, Australia.
8
Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, W12 0NN, UK. Electronic address: g.frost@imperial.ac.uk.
9
Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, W12 0NN, UK; Division of Diabetes and Nutritional Sciences, King's College London, London, SE1 9RT, UK. Electronic address: gavin.bewick@kcl.ac.uk.

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.

KEYWORDS:

Colon; Diet; Microbiota; Obesity; Peptide YY

PMID:
28123937
PMCID:
PMC5220466
DOI:
10.1016/j.molmet.2016.10.011
[Indexed for MEDLINE]
Free PMC Article

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