GPR40/FFA1 Free Fatty Acid Receptors and Their Functional Role

The endogenous ligands of GPR40/FFA1 receptors, which are members of the G protein-coupled receptor class, are saturated and unsaturated free fatty acids (C6–C12) and long-chain (>C12) structures. The highest levels of expression of these receptors are seen in pancreatic β cells and neurons in various parts of the CNS. An enormous amount of experimental data on the functional roles of these receptors in the central and peripheral regulation of the body’s metabolic status has been published since the “deorphanization” of these receptors in 2003. This review summarizes current understanding of the mechanisms regulating GPR40/FFA1 receptors by endogenous and synthetic ligands and the intracellular signal transduction systems activated on exposure to free fatty acids. The mechanisms of GPR40/FFA1-mediated effects of free fatty acids on glucose-stimulated insulin secretion by pancreatic β cells are addressed, along with the production of incretins by enteroendocrine cells; the mechanisms of actions on the support of neurogenesis and neurodifferentiation are also considered. Advances and potentials in the use of synthetic ligands of GPR40/FFA1 receptors in the treatment of metabolic disorders are assessed. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.