Free Fatty Acid Receptors and Drug Discovery

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  • Hirasawa Akira
    Department of Genomic Drug Discovery Science, Kyoto University Graduate School of Pharmaceutical Sciences
  • Hara Takafumi
    Department of Genomic Drug Discovery Science, Kyoto University Graduate School of Pharmaceutical Sciences
  • Katsuma Susumu
    Department of Genomic Drug Discovery Science, Kyoto University Graduate School of Pharmaceutical Sciences
  • Adachi Tetsuya
    Department of Genomic Drug Discovery Science, Kyoto University Graduate School of Pharmaceutical Sciences
  • Tsujimoto Gozoh
    Department of Genomic Drug Discovery Science, Kyoto University Graduate School of Pharmaceutical Sciences

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Utilizing the human genome database, the recently developed G-protein-coupled receptor (GPCR) deorphanizing strategy successfully identified multiple receptors of free fatty acids (FFAs) and is proposed to play a critical role in a variety of physiologic homeostasis mechanisms. GPR40 and GPR120 are activated by medium- and long-chain FFAs, whereas GPR41 and GPR43 are activated by short-chain FFAs. GPR40, which is preferentially expressed in pancreatic β-cells, mediates insulin secretion. On the other hand, GPR120, which is abundantly expressed in the intestine, functions as a receptor for unsaturated long-chain FFAs and promotes the secretion of glucagon-like peptide-1 (GLP-1). In this review, we summarize the identification, structure, and pharmacology of the receptors and speculate on the respective physiologic roles that FFA receptor family members may play.

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