Free fatty acid receptor (FFAR)

Free fatty acid receptors (FFARs) are a class of G protein-coupled receptors that serve as physiological sensors for free fatty acids of different chain lengths, mediating various metabolic and immune functions (IUPHAR/BPS Guide to Pharmacology). The family consists of four primary members: FFAR1 (GPR40) and FFAR4 (GPR120), which are activated by medium- and long-chain fatty acids, and FFAR2 (GPR43) and FFAR3 (GPR41), which are activated by short-chain fatty acids (PubMed: 24011514). FFAR1 is highly expressed in pancreatic beta cells and facilitates glucose-stimulated insulin secretion, making it a prominent target for type 2 diabetes therapy (UniProt: P13945). FFAR4 is found in adipose tissue and macrophages, where it exerts anti-inflammatory effects and improves insulin sensitivity (PubMed: 20811458). These receptors provide a critical link between dietary fat intake and the endocrine system, influencing the release of incretin hormones like GLP-1 (PubMed: 18305450). Despite their therapeutic potential, the development of FFAR agonists has been hindered by safety issues, most notably the drug-induced liver injury observed with the FFAR1 agonist fasiglifam (PubMed: 24635515). Current research is also investigating the role of these receptors in gut health, appetite regulation, and the treatment of non-alcoholic steatohepatitis (NASH).

Other names

G protein-coupled receptor 40G protein-coupled receptor 41G protein-coupled receptor 43G protein-coupled receptor 120G protein-coupled receptor 84FFA receptorGPR40GPR41GPR43GPR120GPR84

Agonism of FFAR1 and FFAR4 to stimulate glucose-dependent insulin secretion and anti-inflammatory pathways; modulation of FFAR2 and FFAR3 to influence gut hormone release and immune cell activity.