Abstract
Free fatty acids (FFAs) are not only essential nutritional components but they also act as signaling molecules in various physiological processes. A strategy to deorphanize G-protein-coupled receptors (GPCRs) identified a series of receptors for FFAs that play significant roles in nutrition regulation. In this free fatty acid receptor family, FFAR1 (GPR40) and FFAR4 (GPR120) are activated by long-chain FFAs. FFAR1 regulates insulin secretion in pancreatic β-cells, whereas FFAR4 promotes the secretion of glucagon-like peptide-1 (GLP-1) in the intestine, and also acts as a lipid sensor in adipose tissue to sense dietary fat and control energy balance. In this review, we discuss recent advances in the pharmacological characterization of FFAR1 and FFAR4, and we present a summary of current understandings of their physiological roles and their potential as drug targets.
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