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

被引：199

作者：

Brooks, Lucy ^{[1
]}

Viardot, Alexander ^{[4
]}

Tsakmaki, Anastasia ^{[2
]}

Stolarczyk, Emilie ^{[2
]}

Howard, Jane K. ^{[2
]}

Cani, Patrice D. ^{[5
]}

Everard, Amandine ^{[5
]}

Sleeth, Michelle L. ^{[1
]}

Psichas, Arianna ^{[1
]}

Anastasovskaj, Jelena ^{[3
]}

Bell, Jimmy D. ^{[3
]}

Bell-Anderson, Kim ^{[6
]}

Mackay, Charles R. ^{[7
,8
]}

Ghatei, Mohammad A. ^{[1
]}

Bloom, Stephen R. ^{[1
]}

Frost, Gary ^{[1
]}

Bewick, Gavin A. ^{[1
,2
]}

机构：

[1] Imperial Coll London, Div Endocrinol Diabet & Metab, London W12 0NN, England

[2] Kings Coll London, Div Diabet & Nutr Sci, London SE1 9RT, England

[3] Imperial Coll London, Metab & Mol Imaging Grp, MRC, Ctr Clin Sci, London W12 0NN, England

[4] Garvan Inst Med Res, Diabet & Metab Div, Sydney, NSW 2010, Australia

[5] Catholic Univ Louvain, Louvain Drug Res Inst, Metab & Nutr Res Grp, WELBIO Walloon Excellence Life Sci & BIOtechnol, B-1200 Brussels, Belgium

[6] Univ Sydney, Sch Mol Biosci, Sydney, NSW 2006, Australia

[7] Univ Sydney, Sydney Med Sch, Charles Perkins Ctr, Sydney, NSW 2006, Australia

[8] Monash Univ, Dept Immunol, Clayton, Vic 3800, Australia

来源：

MOLECULAR METABOLISM | 2017年 / 6卷 / 01期

基金：

美国国家卫生研究院; 英国生物技术与生命科学研究理事会; 英国医学研究理事会; 欧洲研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

Obesity; Diet; Peptide YY; Microbiota; Colon; GLUCAGON-LIKE PEPTIDE-1; FATTY-ACID RECEPTOR; GUT MICROBIOTA; INSULIN SENSITIVITY; OBESITY; GLUCOSE; MICE; YY; DIFFERENTIATION; APPETITE;

D O I：

10.1016/j.molmet.2016.10.011

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (C) 2016 Published by Elsevier GmbH.

引用

页码：48 / 60

页数：13

共 70 条

[21] GLUCAGON-LIKE PEPTIDE-1 CELLS IN THE GASTROINTESTINAL-TRACT AND PANCREAS OF RAT, PIG AND MAN [J].

EISSELE, R ;

GOKE, R ;

WILLEMER, S ;

HARTHUS, HP ;

VERMEER, H ;

ARNOLD, R ;

GOKE, B .

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1992, 22 (04) :283-291

[22] Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells [J].

Engelstoft, Maja S. ;

Park, Won-mee ;

Sakata, Ichiro ;

Kristensen, Line V. ;

Husted, Anna Sofie ;

Osborne-Lawrence, Sherri ;

Piper, Paul K. ;

Walker, Angela K. ;

Pedersen, Maria H. ;

Nohr, Mark K. ;

Pan, Jie ;

Sinz, Christopher J. ;

Carrington, Paul E. ;

Akiyama, Taro E. ;

Jones, Robert M. ;

Tang, Cong ;

Ahmed, Kashan ;

Offermanns, Stefan ;

Egerod, Kristoffer L. ;

Zigman, Jeffrey M. ;

Schwartz, Thue W. .

MOLECULAR METABOLISM, 2013, 2 (04) :376-392

[23] A Gut Feeling for Obesity: 7TM Sensors on Enteroendocrine Cells [J].

Engelstoft, Maja S. ;

Egerod, Kristoffer L. ;

Holst, Birgitte ;

Schwartz, Thue W. .

CELL METABOLISM, 2008, 8 (06) :447-449

[24] Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity [J].

Everard, Amandine ;

Belzer, Clara ;

Geurts, Lucie ;

Ouwerkerk, Janneke P. ;

Druart, Celine ;

Bindels, Laure B. ;

Guiot, Yves ;

Derrien, Muriel ;

Muccioli, Giulio G. ;

Delzenne, Nathalie M. ;

de Vos, Willem M. ;

Cani, Patrice D. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (22) :9066-9071

[25] Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced Leptin-Resistant Mice [J].

Everard, Amandine ;

Lazarevic, Vladimir ;

Derrien, Muriel ;

Girard, Myriam ;

Muccioli, Giulio M. ;

Neyrinck, Audrey M. ;

Possemiers, Sam ;

Van Holle, Arm ;

Francois, Patrice ;

de Vos, Willem M. ;

Delzenne, Nathalie M. ;

Schrenzel, Jacques ;

Cani, Patrice D. .

DIABETES, 2011, 60 (11) :2775-2786

[26] The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism [J].

Frost, Gary ;

Sleeth, Michelle L. ;

Sahuri-Arisoylu, Meliz ;

Lizarbe, Blanca ;

Cerdan, Sebastian ;

Brody, Leigh ;

Anastasovska, Jelena ;

Ghourab, Samar ;

Hankir, Mohammed ;

Zhang, Shuai ;

Carling, David ;

Swann, Jonathan R. ;

Gibson, Glenn ;

Viardot, Alexander ;

Morrison, Douglas ;

Thomas, E. Louise ;

Bell, Jimmy D. .

NATURE COMMUNICATIONS, 2014, 5

[27] Neurotensin Is Coexpressed, Coreleased, and Acts Together With GLP-1 and PYY in Enteroendocrine Control of Metabolism [J].

Grunddal, Kaare V. ;

Ratner, Cecilia F. ;

Svendsen, Berit ;

Sommer, Felix ;

Engelstoft, Maja S. ;

Madsen, Andreas N. ;

Pedersen, Jens ;

Nohr, Mark K. ;

Egerod, Kristoffer L. ;

Nawrocki, Andrea R. ;

Kowalski, Timothy ;

Howard, Andrew D. ;

Poulsen, Steen Seier ;

Offermanns, Stefan ;

Backhed, Fredrik ;

Holst, Jens J. ;

Holst, Birgitte ;

Schwartz, Thue W. .

ENDOCRINOLOGY, 2016, 157 (01) :176-194

[28] Overlap of Endocrine Hormone Expression in the Mouse Intestine Revealed by Transcriptional Profiling and Flow Cytometry [J].

Habib, Abdella M. ;

Richards, Paul ;

Cairns, Lynne S. ;

Rogers, Gareth J. ;

Bannon, Christopher A. M. ;

Parker, Helen E. ;

Morley, Tom C. E. ;

Yeo, Giles S. H. ;

Reimann, Frank ;

Gribble, Fiona M. .

ENDOCRINOLOGY, 2012, 153 (07) :3054-3065

[29] Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons [J].

Hahn, TM ;

Breininger, JF ;

Baskin, DG ;

Schwartz, MW .

NATURE NEUROSCIENCE, 1998, 1 (04) :271-272

[30] Adipose tissue dysfunction in obesity, diabetes, and vascular diseases [J].

Hajer, Gideon R. ;

van Haeften, Timon W. ;

Visseren, Frank L. J. .

EUROPEAN HEART JOURNAL, 2008, 29 (24) :2959-2971

← 1 2 3 4 5 6 7 →