Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders

J Pharm Sci. 2011 Sep;100(9):3594-601. doi: 10.1002/jps.22639. Epub 2011 May 25.


Free fatty acids (FFAs) are not only essential nutritional components, but they also act as signaling molecules in various physiological processes. Recently, a G-protein-coupled receptor deorphanizing strategy has successfully identified a family of receptors that are activated by FFAs. FFA receptors (FFARs) are proposed to play critical roles in a variety of physiological and pathophysiological processes, especially in metabolic disorders. Among the FFARs, FFAR1 (GPR40) and GPR120 are activated by medium- and long-chain FFAs. FFAR1 facilitates glucose-stimulated insulin secretion from pancreatic β-cells, whereas GPR120 regulates the secretion of glucagon-like peptide-1 in the intestine, as well as insulin sensitivity in macrophages. Because these receptors are potential therapeutic targets for metabolic disorders such as type 2 diabetes, selective ligands have been developed. In this review, we discuss recent advances in the identification of ligands, structure activity relationships, and pharmacological characterization of FFAR1 and GPR120, and we present a summary of recent progress in understanding their physiological roles and their potential as drug targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Metabolic Diseases / drug therapy*
  • Receptors, G-Protein-Coupled / drug effects*


  • FFAR1 protein, human
  • FFAR4 protein, human
  • Receptors, G-Protein-Coupled