Overview

Free fatty acid receptors (FFA, nomenclature as agreed by the NC-IUPHAR Subcommittee on free fatty acid receptors [1,2]) are activated by free fatty acids. Long-chain saturated and unsaturated fatty acids... [read more] (including C14.0 (myristic acid), C16:0 (palmitic acid), C18:1 (oleic acid), C18:2 (linoleic acid), C18:3, (α-linolenic acid), C20:4 (arachidonic acid), C20:5,n-3 (EPA) and C22:6,n-3 (docosahexaenoic acid)) activate FFA1 [3,4,5] and FFA4 receptors [6,7,8], while short chain fatty acids (C2 (acetic acid), C3 (propanoic acid), C4 (butyric acid) and C5 (pentanoic acid)) activate FFA2 [9,10,11] and FFA3 [9,10] receptors. The crystal structure for agonist bound FFA1 has been described [12].

References

1. Stoddart LA, Smith NJ, Milligan G. International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions. Pharmacol Rev 2008;60:405-17.
2. Davenport AP, Alexander SP, Sharman JL, et al. International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol Rev 2013;65:967-86.
3. Briscoe CP, Tadayyon M, Andrews JL, et al. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J Biol Chem 2003;278:11303-11.
4. Itoh Y, Kawamata Y, Harada M, et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 2003;422:173-6.
5. Kotarsky K, Nilsson NE, Flodgren E, et al. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs. Biochem Biophys Res Commun 2003;301:406-10.
6. Hirasawa A, Tsumaya K, Awaji T, et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 2005;11:90-94.
7. Ichimura A, Hirasawa A, Poulain-Godefroy O, et al. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature 2012;483:350-4.
8. Oh DY, Talukdar S, Bae EJ, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010;142:687-98.
9. Brown AJ, Goldsworthy SM, Barnes AA, et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003;278:11312-9.
10. Le Poul E, Loison C, Struyf S, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 2003;278:25481-9.
11. Nilsson NE, Kotarsky K, Owman C, et al. 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.
12. Srivastava A, Yano J, Hirozane Y, et al. High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875. Nature 2014;513:124-7.

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