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Free Fatty Acid Receptor Family

The free fatty acid receptor (FFAR) is a G-protein coupled receptor which is activated by free fatty acids (FFAs) and binds free fatty acids. FFARs have been identified by a strategy of the GPCR deorphanization derived from the Human Genome Database. FFARs are essential in physiological processes and various pathophysiological processes. It plays an important role not only as essential nutritional components but also as signaling molecules in numerous physiological processes. FFARs act as a physiological sensor of food-derived free fatty acids and digestion products in the gastrointestinal tract. In addition, they are thought to be involved in modulating energy metabolism mediated by the secretion of insulin and incretin hormones. It also regulates the sympathetic nervous system, taste preferences and inflammatory responses associated with insulin resistance. FFARs have been used for the treatment of metabolic diseases including type 2 diabetes and metabolic syndrome.

Effects of fatty acids (including SC- and LCFAs) derived from the diet by gut microbiota on the regulation of host metabolic and immune functions.Fig.1 Effects of fatty acids (including SC- and LCFAs) derived from the diet by gut microbiota on the regulation of host metabolic and immune functions. (Miyamoto, et al. 2016)

Several FFARs have been identified and used as key components of various physiological processes. Here shows part of fatty acid receptors in humans including FFAR1, FFAR2, FFAR3, FFAR4, which are four variants of the receptor, each encoded by a separate gene (FFAR1, FFAR2, FFAR3, FFAR4). FFARs are categorized according to the chain length of the FFA ligands that activate each FFAR. FFA2 and FFA3 are activated by short-chain FFAs. GPR84 is activated by medium chain FFAs, and FFA1 and GPR120 are activated by medium or long chain FFAs. FFAR2 and FFAR3 may interact to form the FFAR2-FFAR3 receptor heteromer.

Human Free Fatty Acid Receptor Members
FFAR1 FFAR2 FFAR3 FFAR4

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Reference

  1. Miyamoto J, et al. (2016). Nutritional Signaling via Free Fatty Acid Receptors. Int J Mol Sci. 17(4): 450.

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