Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders
✍ Scribed by Takafumi Hara; Akira Hirasawa; Atsuhiko Ichimura; Ikuo Kimura; Gozoh Tsujimoto
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 180 KB
- Volume
- 100
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
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 $-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.