Ffar2

Summary

Gene Symbol: Ffar2
Description: free fatty acid receptor 2
Alias: GPCR43, Gpr43, free fatty acid receptor 2, G protein-coupled receptor 43, leukocyte-specific STAT-induced GPCR
Species: mouse
Products:     Ffar2

Top Publications

  1. Hong Y, Nishimura Y, Hishikawa D, Tsuzuki H, Miyahara H, Gotoh C, et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology. 2005;146:5092-9 pubmed
    ..The objective of this study was to investigate the involvement of GPCR41, GPCR43, and their ligands in the process of adipogenesis...
  2. Bjursell M, Admyre T, Göransson M, Marley A, Smith D, Oscarsson J, et al. Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet. Am J Physiol Endocrinol Metab. 2011;300:E211-20 pubmed publisher
    b>Free fatty acid receptor 2 (Ffar2), also known as GPR43, is activated by short-chain fatty acids (SCFA) and expressed in intestine, adipocytes, and immune cells, suggesting involvement in lipid and immune regulation...
  3. Tolhurst G, Heffron H, Lam Y, Parker H, Habib A, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61:364-71 pubmed publisher
    ..Quantitative PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1-secreting L cells, and consistent with the reported coupling of GPR43 to Gq ..
  4. Hudson B, Tikhonova I, Pandey S, Ulven T, Milligan G. Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3. J Biol Chem. 2012;287:41195-209 pubmed publisher
    ..Reciprocal mutation of these residues between species orthologs resulted in the induction (or repression) of constitutive activity and in most cases also yielded corresponding changes in SCFA potency. ..
  5. Ge H, Li X, Weiszmann J, Wang P, Baribault H, Chen J, et al. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology. 2008;149:4519-26 pubmed publisher
    G protein-coupled receptor 43 (GPR43) has been identified as a receptor for short-chain fatty acids that include acetate and propionate...
  6. Maslowski K, Vieira A, Ng A, Kranich J, Sierro F, Yu D, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282-6 pubmed publisher
    ..SCFAs bind the G-protein-coupled receptor 43 (GPR43, also known as FFAR2), and here we show that SCFA-GPR43 interactions profoundly affect inflammatory responses...
  7. Sina C, Gavrilova O, Förster M, Till A, Derer S, Hildebrand F, et al. G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J Immunol. 2009;183:7514-22 pubmed publisher
    ..The functional role of GPR43 activation for in vivo orchestration of immune response is unclear...
  8. Kimura I, Inoue D, Maeda T, Hara T, Ichimura A, Miyauchi S, et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci U S A. 2011;108:8030-5 pubmed publisher
    ..These findings establish that SCFAs and ketone bodies directly regulate GPR41-mediated SNS activity and thereby control body energy expenditure in maintaining metabolic homeostasis. ..
  9. Vinolo M, Ferguson G, Kulkarni S, Damoulakis G, Anderson K, Bohlooly Y M, et al. SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor. PLoS ONE. 2011;6:e21205 pubmed publisher
    ..Some of these effects have been suggested to occur through the direct actions of SCFAs on the GPR43 receptor in neutrophils, though the precise role of this receptor in neutrophil activation is still unclear...

More Information

Publications38

  1. Nilsson N, Kotarsky K, Owman C, Olde B. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem Biophys Res Commun. 2003;303:1047-52 pubmed
    ..We have cloned the previously described putative orphan G-protein coupled receptor, GPR43, and have functionally identified SCFA as the activating ligands...
  2. Pan P, W Skaer C, Wang H, Oshima K, Huang Y, Yu J, et al. Loss of free fatty acid receptor 2 enhances colonic adenoma development and reduces the chemopreventive effects of black raspberries in ApcMin/+ mice. Carcinogenesis. 2017;38:86-93 pubmed publisher
    ..The current study investigated the role of free fatty acid receptor 2 (FFAR2) in colon carcinogenesis and whether the FFAR2 signaling pathway contributes to BRB-mediated ..
  3. Smith P, Howitt M, Panikov N, Michaud M, Gallini C, Bohlooly Y M, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341:569-73 pubmed publisher
    ..fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice...
  4. Tang C, Ahmed K, Gille A, Lu S, Gröne H, Tunaru S, et al. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat Med. 2015;21:173-7 pubmed publisher
    ..Here we demonstrate that the short-chain fatty acid receptors FFA2 (encoded by FFAR2) and FFA3 (encoded by FFAR3) are expressed in mouse and human pancreatic beta cells and mediate an inhibition of ..
  5. Villa S, Priyadarshini M, Fuller M, Bhardwaj T, Brodsky M, Angueira A, et al. Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival. Sci Rep. 2016;6:28159 pubmed publisher
    ..b>Free Fatty Acid Receptor 2 (FFA2) is a β cell-expressed GPCR that is activated by short chain fatty acids, particularly acetate...
  6. Hudson B, Due Hansen M, Christiansen E, Hansen A, MacKenzie A, Murdoch H, et al. Defining the molecular basis for the first potent and selective orthosteric agonists of the FFA2 free fatty acid receptor. J Biol Chem. 2013;288:17296-312 pubmed publisher
  7. Senga T, Iwamoto S, Yoshida T, Yokota T, Adachi K, Azuma E, et al. LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3. Blood. 2003;101:1185-7 pubmed
    ..STAT-induced GPCR (LSSIG), which is a novel murine orphan GPCR with the highest homology to human GPR43. The mRNA expression of LSSIG was clearly induced in M1 leukemia cells during the leukemia inhibitory factor (LIF)-..
  8. Erny D, HrabÄ› de Angelis A, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18:965-77 pubmed publisher
    ..Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions...
  9. Bindels L, Porporato P, Ducastel S, Sboarina M, Neyrinck A, Dewulf E, et al. Ffar2 expression regulates leukaemic cell growth in vivo. Br J Cancer. 2017;117:1336-1340 pubmed publisher
    Activation of free fatty acid receptor 2 (FFAR2) by microbiota-derived metabolites (e.g., propionate) reduces leukaemic cell proliferation in vitro...
  10. D Souza W, Douangpanya J, Mu S, Jaeckel P, Zhang M, Maxwell J, et al. Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses. PLoS ONE. 2017;12:e0180190 pubmed publisher
    ..It has been shown that short chain fatty acids (SCFAs) are protective in IBD and that GPR43 mediates the protective effects of SCFAs...
  11. Wu W, Sun M, Chen F, Cao A, Liu H, Zhao Y, et al. Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43. Mucosal Immunol. 2017;10:946-956 pubmed publisher
    ..short-chain fatty acid acetate promoted intestinal IgA responses, which was mediated by "metabolite-sensing" GPR43. GPR43-/- mice demonstrated lower levels of intestinal IgA and IgA+ gut bacteria compared ..
  12. Kamp M, Shim R, Nicholls A, Oliveira A, Mason L, Binge L, et al. G Protein-Coupled Receptor 43 Modulates Neutrophil Recruitment during Acute Inflammation. PLoS ONE. 2016;11:e0163750 pubmed publisher
    ..One of the main SCFA receptors, GPR43, is highly expressed by neutrophils, which suggests that the actions of GPR43 and dietary fibre intake may affect ..
  13. Agus A, Denizot J, Thévenot J, Martinez Medina M, Massier S, Sauvanet P, et al. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation. Sci Rep. 2016;6:19032 pubmed publisher
    ..coli, a decrease in protective bacteria, and a significantly decreased of SCFA concentrations. The expression of GPR43, a SCFA receptor was reduced in mice treated with a HF/HS diet and reduced in CD patients compared with controls...
  14. Macia L, Tan J, Vieira A, Leach K, Stanley D, Luong S, et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat Commun. 2015;6:6734 pubmed publisher
    ..SCFAs binding to the 'metabolite-sensing' receptors GPR43 and GPR109A in non-haematopoietic cells mediate these protective effects...
  15. Tan J, McKenzie C, Vuillermin P, Goverse G, Vinuesa C, Mebius R, et al. Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways. Cell Rep. 2016;15:2809-24 pubmed publisher
    ..Mice lacking GPR43 or GPR109A, receptors for SCFAs, showed exacerbated food allergy and fewer CD103(+) DCs...
  16. Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013;4:1829 pubmed publisher
    ..Here we show that the short-chain fatty acid receptor GPR43 links the metabolic activity of the gut microbiota with host body energy homoeostasis...
  17. Dewulf E, Cani P, Neyrinck A, Possemiers S, Van Holle A, Muccioli G, et al. Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPAR?-related adipogenesis in the white adipose tissue of high-fat diet-fed mice. J Nutr Biochem. 2011;22:712-22 pubmed publisher
    ..influence of ITF supplementation on adipose tissue metabolism, by focusing on a G protein-coupled receptor (GPR), GPR43, as a potential link between gut fermentation processes and white adipose tissue development...
  18. Priyadarshini M, Villa S, Fuller M, Wicksteed B, Mackay C, Alquier T, et al. An Acetate-Specific GPCR, FFAR2, Regulates Insulin Secretion. Mol Endocrinol. 2015;29:1055-66 pubmed publisher
    ..The short-chain fatty acid-sensing G protein-coupled receptor, free fatty acid receptor 2 (FFAR2), is expressed in pancreatic ?-cells, and in rodents, its expression is altered during insulin ..
  19. Fuller M, Priyadarshini M, Gibbons S, Angueira A, Brodsky M, Hayes M, et al. The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis. Am J Physiol Endocrinol Metab. 2015;309:E840-51 pubmed publisher
    ..as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene (Ffar2) expression is higher in pancreatic islets during pregnancy...
  20. Kim M, Kang S, Park J, Yanagisawa M, Kim C. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology. 2013;145:396-406.e1-10 pubmed publisher
    ..microbial metabolites in the intestine, activate cells via G-protein-coupled receptors (GPRs), such as GPR41 and GPR43. We studied regulation of the immune response by SCFAs and their receptors in the intestines of mice...
  21. Fuller M, Li X, Fisch R, Bughara M, Wicksteed B, Kovatcheva Datchary P, et al. FFA2 Contribution to Gestational Glucose Tolerance Is Not Disrupted by Antibiotics. PLoS ONE. 2016;11:e0167837 pubmed publisher
    During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion ..
  22. Nadeem A, Ahmad S, Al Harbi N, El Sherbeeny A, Al Harbi M, Almukhlafi T. GPR43 activation enhances psoriasis-like inflammation through epidermal upregulation of IL-6 and dual oxidase 2 signaling in a murine model. Cell Signal. 2017;33:59-68 pubmed publisher
    ..b>GPR43 is one of the receptors to sense short-chain fatty acids, and expressed in various immune and non-immune cells...
  23. McNelis J, Lee Y, Mayoral R, van der Kant R, Johnson A, Wollam J, et al. GPR43 Potentiates β-Cell Function in Obesity. Diabetes. 2015;64:3203-17 pubmed publisher
    ..Here we identify GPR43, a receptor for bacterially produced short-chain fatty acids (SCFAs), as a modulator of microbiota-host ..
  24. Vieira A, Macia L, Galvão I, Martins F, Canesso M, Amaral F, et al. A Role for Gut Microbiota and the Metabolite-Sensing Receptor GPR43 in a Murine Model of Gout. Arthritis Rheumatol. 2015;67:1646-56 pubmed publisher
    ..study was undertaken to investigate the relevance of gut microbiota, acetate, and the metabolite-sensing receptor GPR43 in regulating inflammation in a murine model of gout...
  25. Nøhr M, Pedersen M, Gille A, Egerod K, Engelstoft M, Husted A, et al. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology. 2013;154:3552-64 pubmed publisher
    The expression of short-chain fatty acid receptors GPR41/FFAR3 and GPR43/ free fatty acid receptor 2 (FFAR2) was studied in the gastrointestinal tract of transgenic monomeric red fluorescent protein (mRFP) reporter mice...
  26. Nakajima A, Nakatani A, Hasegawa S, Irie J, Ozawa K, Tsujimoto G, et al. The short chain fatty acid receptor GPR43 regulates inflammatory signals in adipose tissue M2-type macrophages. PLoS ONE. 2017;12:e0179696 pubmed publisher
    ..G-protein-coupled receptor 43 (GPR43), which is activated by short-chain fatty acids (SCFAs), is known to be most abundantly expressed in white adipose ..
  27. Li Y, Kokrashvili Z, Mosinger B, Margolskee R. Gustducin couples fatty acid receptors to GLP-1 release in colon. Am J Physiol Endocrinol Metab. 2013;304:E651-60 pubmed publisher
    ..Gustducin also was coexpressed with fatty acid G protein-coupled receptor (GPR) 40, GPR41, GPR43, GPR119, GPR120, and bile acid G protein-coupled receptor TGR5 in enteroendocrine cells of the colon...
  28. Bolognini D, Moss C, Nilsson K, Petersson A, Donnelly I, Sergeev E, et al. A Novel Allosteric Activator of Free Fatty Acid 2 Receptor Displays Unique Gi-functional Bias. J Biol Chem. 2016;291:18915-31 pubmed publisher
  29. Mariño E, Richards J, McLeod K, Stanley D, Yap Y, Knight J, et al. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol. 2017;18:552-562 pubmed publisher
    ..Medicinal foods or metabolites might represent an effective and natural approach for countering the numerous immunological defects that contribute to T cell-dependent autoimmune diseases. ..