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

Lucy Brooks, Alexander Viardot, Anastasia Tsakmaki, Emilie Stolarczyk, Jane K. Howard, Patrice D. Cani, Amandine Everard, Michelle L. Sleeth, Arianna Psichas, Jelena Anastasovskaj, Jimmy D. Bell, Kim Bell-Anderson, Charles R. Mackay, Mohammad A Ghatei, Stephen R. Bloom, Gary Frost, Gavin A. Bewick

Research output: Contribution to journalArticleResearchpeer-review

59 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)48-60
Number of pages13
JournalMolecular Metabolism
Volume6
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • Colon
  • Diet
  • Microbiota
  • Obesity
  • Peptide YY

Cite this

Brooks, L., Viardot, A., Tsakmaki, A., Stolarczyk, E., Howard, J. K., Cani, P. D., ... Bewick, G. A. (2017). Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety. Molecular Metabolism, 6(1), 48-60. https://doi.org/10.1016/j.molmet.2016.10.011
Brooks, Lucy ; Viardot, Alexander ; Tsakmaki, Anastasia ; Stolarczyk, Emilie ; Howard, Jane K. ; Cani, Patrice D. ; Everard, Amandine ; Sleeth, Michelle L. ; Psichas, Arianna ; Anastasovskaj, Jelena ; Bell, Jimmy D. ; Bell-Anderson, Kim ; Mackay, Charles R. ; Ghatei, Mohammad A ; Bloom, Stephen R. ; Frost, Gary ; Bewick, Gavin A. / Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety. In: Molecular Metabolism. 2017 ; Vol. 6, No. 1. pp. 48-60.
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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.",
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author = "Lucy Brooks and Alexander Viardot and Anastasia Tsakmaki and Emilie Stolarczyk and Howard, {Jane K.} and Cani, {Patrice D.} and Amandine Everard and Sleeth, {Michelle L.} and Arianna Psichas and Jelena Anastasovskaj and Bell, {Jimmy D.} and Kim Bell-Anderson and Mackay, {Charles R.} and Ghatei, {Mohammad A} and Bloom, {Stephen R.} and Gary Frost and Bewick, {Gavin A.}",
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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 2017, 'Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety', Molecular Metabolism, vol. 6, no. 1, pp. 48-60. https://doi.org/10.1016/j.molmet.2016.10.011

Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety. / Brooks, Lucy; Viardot, Alexander; Tsakmaki, Anastasia; Stolarczyk, Emilie; Howard, Jane K.; Cani, Patrice D.; Everard, Amandine; Sleeth, Michelle L.; Psichas, Arianna; Anastasovskaj, Jelena; Bell, Jimmy D.; Bell-Anderson, Kim; Mackay, Charles R.; Ghatei, Mohammad A; Bloom, Stephen R.; Frost, Gary; Bewick, Gavin A.

In: Molecular Metabolism, Vol. 6, No. 1, 01.01.2017, p. 48-60.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety

AU - Brooks, Lucy

AU - Viardot, Alexander

AU - Tsakmaki, Anastasia

AU - Stolarczyk, Emilie

AU - Howard, Jane K.

AU - Cani, Patrice D.

AU - Everard, Amandine

AU - Sleeth, Michelle L.

AU - Psichas, Arianna

AU - Anastasovskaj, Jelena

AU - Bell, Jimmy D.

AU - Bell-Anderson, Kim

AU - Mackay, Charles R.

AU - Ghatei, Mohammad A

AU - Bloom, Stephen R.

AU - Frost, Gary

AU - Bewick, Gavin A.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

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KW - Diet

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