Biology:Free fatty acid receptor 2

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Free fatty acid receptor 2 (FFA2) is a G-protein coupled receptor encoded by the FFAR2 gene.[1][2][3] It is a member of the free fatty acid receptors group of receptors.

Expression

FFAR2 mRNA is expressed in adipose tissue, pancreas, spleen, lymph nodes, bone marrow, and peripheral blood mononuclear cells.[4][5] FFAR2 transcription is regulated by the XBP1 transcription factor which binds to the core promoter.[6]

Function

Mouse studies utilizing Ffar2 gene deletions have implicated the receptor in the regulation of energy metabolism and immune responses.[7] Short-chain fatty acids (SCFA's) generated in the processing of fiber by intestinal microbiota act as ligands for the receptor and can affect neutrophil chemotaxis.[8][9] However, discrepancies between the pathways activated by FFAR2 agonists in human cells and the equivalent murine counterparts have been observed.[10][11][12]

Heteromerization

FFA2 may interact with FFAR3 to form a FFAR2-FFAR3 receptor heteromer with signalling that is distinct from the parent homomers.[13]

See also

References

  1. ↑ "International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions". Pharmacological Reviews 60 (4): 405–17. December 2008. doi:10.1124/pr.108.00802. PMID 19047536. 
  2. ↑ "FFA2 receptor | Free fatty acid receptors". IUPHAR/BPS Guide to PHARMACOLOGY. https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=226. 
  3. ↑ "Entrez Gene: FFAR2 free fatty acid receptor 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2867. 
  4. ↑ "Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids". Biochemical and Biophysical Research Communications 303 (4): 1047–52. April 2003. doi:10.1016/S0006-291X(03)00488-1. PMID 12684041. 
  5. ↑ "Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation". The Journal of Biological Chemistry 278 (28): 25481–9. July 2003. doi:10.1074/jbc.M301403200. PMID 12711604. 
  6. ↑ "The short-chain fatty acid receptor GPR43 is transcriptionally regulated by XBP1 in human monocytes". Scientific Reports 5: 8134. January 2015. doi:10.1038/srep08134. PMID 25633224. 
  7. ↑ "GPR43/FFA2: physiopathological relevance and therapeutic prospects". Trends in Pharmacological Sciences 34 (4): 226–32. April 2013. doi:10.1016/j.tips.2013.02.002. PMID 23489932. 
  8. ↑ "Implication of G Protein-Coupled Receptor 43 in Intestinal Inflammation: A Mini-Review". Frontiers in Immunology 9: 1434. 2018. doi:10.3389/fimmu.2018.01434. PMID 29988393. 
  9. ↑ "Differing roles for short chain fatty acids and GPR43 agonism in the regulation of intestinal barrier function and immune responses". PLOS ONE 12 (7): e0180190. 2017-07-20. doi:10.1371/journal.pone.0180190. PMID 28727837. 
  10. ↑ "Evaluation of the relationship between GPR43 and adiposity in human". Nutrition & Metabolism 10 (1): 11. January 2013. doi:10.1186/1743-7075-10-11. PMID 23327542. 
  11. ↑ "An Acetate-Specific GPCR, FFAR2, Regulates Insulin Secretion". Molecular Endocrinology 29 (7): 1055–66. July 2015. doi:10.1210/me.2015-1007. PMID 26075576. 
  12. ↑ "Human and mouse monocytes display distinct signalling and cytokine profiles upon stimulation with FFAR2/FFAR3 short-chain fatty acid receptor agonists". Scientific Reports 6: 34145. September 2016. doi:10.1038/srep34145. PMID 27667443. 
  13. ↑ "FFAR2-FFAR3 receptor heteromerization modulates short-chain fatty acid sensing". FASEB Journal 32 (1): 289–303. January 2018. doi:10.1096/fj.201700252RR. PMID 28883043. 

Further reading

  • "A family of fatty acid binding receptors". DNA and Cell Biology 24 (1): 54–61. January 2005. doi:10.1089/dna.2005.24.54. PMID 15684720. 
  • "A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1". Biochemical and Biophysical Research Communications 239 (2): 543–7. October 1997. doi:10.1006/bbrc.1997.7513. PMID 9344866. 
  • "LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3". Blood 101 (3): 1185–7. February 2003. doi:10.1182/blood-2002-06-1881. PMID 12393494. 
  • "The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids". The Journal of Biological Chemistry 278 (13): 11312–9. March 2003. doi:10.1074/jbc.M211609200. PMID 12496283. 
  • "Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids". Biochemical and Biophysical Research Communications 303 (4): 1047–52. April 2003. doi:10.1016/S0006-291X(03)00488-1. PMID 12684041. 
  • "Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation". The Journal of Biological Chemistry 278 (28): 25481–9. July 2003. doi:10.1074/jbc.M301403200. PMID 12711604. 
  • "Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast cancer cell line". Cellular Signalling 19 (1): 185–93. January 2007. doi:10.1016/j.cellsig.2006.06.004. PMID 16887331. 

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