title: Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety.
abstract: 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.
  
  
  
  Wild-type orFfar2-/-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 thein vivofindings.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, W12 0NN, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Brooks
authors.affiliation: Diabetes & Metabolism Division, Garvan Institute of Medical Research, Sydney-Darlinghurst, NSW, 2010, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Viardot
authors.affiliation: Division of Diabetes and Nutritional Sciences, King's College London, London, SE1 9RT, UK.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Tsakmaki
authors.affiliation: Division of Diabetes and Nutritional Sciences, King's College London, London, SE1 9RT, UK.
authors.forename: Emilie
authors.initials: E
authors.lastname: Stolarczyk
authors.affiliation: Division of Diabetes and Nutritional Sciences, King's College London, London, SE1 9RT, UK.
authors.forename: Jane K
authors.initials: JK
authors.lastname: Howard
authors.affiliation: 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.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: 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.
authors.forename: Amandine
authors.initials: A
authors.lastname: Everard
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, W12 0NN, UK.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Sleeth
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, W12 0NN, UK.
authors.forename: Arianna
authors.initials: A
authors.lastname: Psichas
authors.affiliation: Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London, W12 0NN, UK.
authors.forename: Jelena
authors.initials: J
authors.lastname: Anastasovskaj
authors.affiliation: Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London, W12 0NN, UK.
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Bell
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Bell-Anderson
authors.affiliation: Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia; Department of Immunology, Monash University, Clayton, VIC, 3800, Australia.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Mackay
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, W12 0NN, UK.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, W12 0NN, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, W12 0NN, UK. Electronic address: g.frost@imperial.ac.uk.
authors.forename: Gary
authors.initials: G
authors.lastname: Frost
authors.affiliation: 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.
authors.forename: Gavin A
authors.initials: GA
authors.lastname: Bewick
mesh_terms: D000818:Animals; D001835:Body Weight; D003106:Colon / Q000166:cytology; D004040:Dietary Carbohydrates / Q000378:metabolism*; D019587:Dietary Supplements; D004435:Eating; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005285:Fermentation; D000074421:Fermented Foods; D005768:Gastrointestinal Hormones / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D007444:Inulin / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism; D019894:Peptide YY / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology; D015430:Weight Gain; D043562:Receptors, G-Protein-Coupled
chemical_list: D004040:Dietary Carbohydrates; D005232:Fatty Acids, Volatile; D005768:Gastrointestinal Hormones; D052216:Glucagon-Like Peptide 1; D007444:Inulin; D019894:Peptide YY; D011956:Receptors, Cell Surface; C473103:FFAR2 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: Colon; Diet; Microbiota; Obesity; Peptide YY