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Prostaglandins Other Lipid Mediat. 2009 Sep;89(3-4):82-8. doi: 10.1016/j.prostaglandins.2009.05.003. Epub 2009 May 19.

Free fatty acid receptors act as nutrient sensors to regulate energy homeostasis.

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Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.


Free fatty acids (FFAs) have been demonstrated to act as ligands of several G-protein-coupled receptors (GPCRs) (FFAR1, FFAR2, FFAR3, GPR84, and GPR120). These fatty acid receptors are proposed to play critical roles in a variety of types of physiological homeostasis. FFAR1 and GPR120 are activated by medium- and long-chain FFAs. GPR84 is activated by medium-chain, but not long-chain, FFAs. In contrast, FFAR2 and FFAR3 are activated by short-chain FFAs. FFAR1 is expressed mainly in pancreatic beta-cells and mediates insulin secretion, whereas GPR120 is expressed abundantly in the intestine and promotes the secretion of glucagon-like peptide-1 (GLP-1). FFAR3 is expressed in enteroendocrine cells and regulates host energy balance through effects that are dependent upon the gut microbiota. In this review, we summarize the identification, structure, and pharmacology of these receptors and present an essential overview of the current understanding of their physiological roles.

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