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

TY - JOUR

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

Y1 - 2017/1

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.

KW - Obesity

KW - Diet

KW - Peptide YY

KW - Microbiota

KW - Colon

U2 - 10.1016/j.molmet.2016.10.011

DO - 10.1016/j.molmet.2016.10.011

M3 - Article

C2 - 28123937

SN - 2212-8778

VL - 6

SP - 48

EP - 60

JO - Molecular Metabolism

JF - Molecular Metabolism

IS - 1

ER -