GPR43/FFA2: physiopathological relevance and therapeutic prospects

被引:172
作者
Bindels, Laure B. [1 ]
Dewulf, Evelyne M. [1 ]
Delzenne, Nathalie M. [1 ]
机构
[1] Catholic Univ Louvain, Louvain Drug Res Inst, Metab & Nutr Res Grp, B-1200 Brussels, Belgium
关键词
CHAIN FATTY-ACIDS; PROTEIN-COUPLED RECEPTOR; GLUCAGON-LIKE PEPTIDE-1; GUT MICROBIOTA; FUNCTIONAL-CHARACTERIZATION; SPECIES ORTHOLOGS; MICE; DIET; GPR41; IDENTIFICATION;
D O I
10.1016/j.tips.2013.02.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Research interest in free fatty acid-binding receptors has been growing during the past decade, with an aim to better understand the modulation of host physiology in response to nutrition. G-protein-coupled receptor 43 (GPR43), also called free fatty acid receptor 2 (FFA2/FFAR2), binds short-chain fatty acids (SCFAs) produced by the microbial fermentation of carbohydrates and has shown promising therapeutic potential. This review presents current knowledge regarding the pharmacological properties of GPR43 and addresses its functions in selected organs (adipose tissue, intestine and immune cells). Furthermore, the demonstration of GPR43 involvement in several pathological conditions such as obesity, inflammatory disease, and cancer suggests new fields of interest related to this receptor. Finally, GPR43 could be a key player in gut microbes host crosstalk, although further research is needed to clearly evaluate its role in the management of host health by nutrients or treatments targeting the gut microbiota.
引用
收藏
页码:226 / 232
页数:7
相关论文
共 60 条
[31]   Identification and Functional Characterization of Allosteric Agonists for the G Protein-Coupled Receptor FFA2 [J].
Lee, Taeweon ;
Schwandner, Ralf ;
Swaminath, Gayathri ;
Weiszmann, Jennifer ;
Cardozo, Mario ;
Greenberg, Joanne ;
Jaeckel, Peter ;
Ge, Hongfei ;
Wang, Yingcai ;
Jiao, Xianyun ;
Liu, Jiwen ;
Kayser, Frank ;
Tian, Hui ;
Li, Yang .
MOLECULAR PHARMACOLOGY, 2008, 74 (06) :1599-1609
[32]   Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43 [J].
Maslowski, Kendle M. ;
Vieira, Angelica T. ;
Ng, Aylwin ;
Kranich, Jan ;
Sierro, Frederic ;
Yu, Di ;
Schilter, Heidi C. ;
Rolph, Michael S. ;
Mackay, Fabienne ;
Artis, David ;
Xavier, Ramnik J. ;
Teixeira, Mauro M. ;
Mackay, Charles R. .
NATURE, 2009, 461 (7268) :1282-U119
[33]   Fecal Butyrate Levels Vary Widely among Individuals but Are Usually Increased by a Diet High in Resistant Starch [J].
McOrist, Alexandra L. ;
Miller, Rosalind B. ;
Bird, Anthony R. ;
Keogh, Jennifer B. ;
Noakes, Manny ;
Topping, David L. ;
Conlon, Michael A. .
JOURNAL OF NUTRITION, 2011, 141 (05) :883-889
[34]   Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids [J].
Nilsson, NE ;
Kotarsky, K ;
Owman, C ;
Olde, B .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 303 (04) :1047-1052
[35]   A human gut microbial gene catalogue established by metagenomic sequencing [J].
Qin, Junjie ;
Li, Ruiqiang ;
Raes, Jeroen ;
Arumugam, Manimozhiyan ;
Burgdorf, Kristoffer Solvsten ;
Manichanh, Chaysavanh ;
Nielsen, Trine ;
Pons, Nicolas ;
Levenez, Florence ;
Yamada, Takuji ;
Mende, Daniel R. ;
Li, Junhua ;
Xu, Junming ;
Li, Shaochuan ;
Li, Dongfang ;
Cao, Jianjun ;
Wang, Bo ;
Liang, Huiqing ;
Zheng, Huisong ;
Xie, Yinlong ;
Tap, Julien ;
Lepage, Patricia ;
Bertalan, Marcelo ;
Batto, Jean-Michel ;
Hansen, Torben ;
Le Paslier, Denis ;
Linneberg, Allan ;
Nielsen, H. Bjorn ;
Pelletier, Eric ;
Renault, Pierre ;
Sicheritz-Ponten, Thomas ;
Turner, Keith ;
Zhu, Hongmei ;
Yu, Chang ;
Li, Shengting ;
Jian, Min ;
Zhou, Yan ;
Li, Yingrui ;
Zhang, Xiuqing ;
Li, Songgang ;
Qin, Nan ;
Yang, Huanming ;
Wang, Jian ;
Brunak, Soren ;
Dore, Joel ;
Guarner, Francisco ;
Kristiansen, Karsten ;
Pedersen, Oluf ;
Parkhill, Julian ;
Weissenbach, Jean .
NATURE, 2010, 464 (7285) :59-U70
[36]   Prebiotic effects: metabolic and health benefits [J].
Roberfroid, Marcel ;
Gibson, Glenn R. ;
Hoyles, Lesley ;
McCartney, Anne L. ;
Rastall, Robert ;
Rowland, Ian ;
Wolvers, Danielle ;
Watzl, Bernhard ;
Szajewska, Hania ;
Stahl, Bernd ;
Guarner, Francisco ;
Respondek, Frederique ;
Whelan, Kevin ;
Coxam, Veronique ;
Davicco, Marie-Jeanne ;
Leotoing, Laurent ;
Wittrant, Yohann ;
Delzenne, Nathalie M. ;
Cani, Patrice D. ;
Neyrinck, Audrey M. ;
Meheust, Agnes .
BRITISH JOURNAL OF NUTRITION, 2010, 104 :S1-S63
[37]   The Role of the Gastrointestinal Microbiota in Colorectal Cancer [J].
Rowland, Ian R. .
CURRENT PHARMACEUTICAL DESIGN, 2009, 15 (13) :1524-1527
[38]   Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41 [J].
Samuel, Buck S. ;
Shaito, Abdullah ;
Motoike, Toshiyuki ;
Rey, Federico E. ;
Backhed, Fredrik ;
Manchester, Jill K. ;
Hammer, Robert E. ;
Williams, S. Clay ;
Crowley, Jan ;
Yanagisawa, Masashi ;
Gordon, Jeffrey I. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (43) :16767-16772
[39]  
Saniere L. R. M., 2012, Patent No. [WO/2012/098033, 2012098033]
[40]   Selective Orthosteric Free Fatty Acid Receptor 2 (FFA2) Agonists IDENTIFICATION OF THE STRUCTURAL AND CHEMICAL REQUIREMENTS FOR SELECTIVE ACTIVATION OF FFA2 VERSUS FFA3 [J].
Schmidt, Johannes ;
Smith, Nicola J. ;
Christiansen, Elisabeth ;
Tikhonova, Irina G. ;
Grundmann, Manuel ;
Hudson, Brian D. ;
Ward, Richard J. ;
Drewke, Christel ;
Milligan, Graeme ;
Kostenis, Evi ;
Ulven, Trond .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (12) :10628-10640