Free fatty acid receptor 4 (GPR120) (FFAR4)

Free fatty acid receptor 4 (FFAR4), also known as GPR120, is a Class A G protein-coupled receptor that acts as a primary sensor for long-chain polyunsaturated fatty acids (PUFAs), such as omega-3 fatty acids like docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). It is highly expressed in the gastrointestinal tract, adipose tissue, and various immune cells, particularly pro-inflammatory macrophages. Functionally, FFAR4 plays a critical role in metabolic homeostasis by stimulating the secretion of incretin hormones like glucagon-like peptide-1 (GLP-1) and promoting insulin-sensitizing effects in adipocytes. Furthermore, it exerts potent anti-inflammatory actions through a beta-arrestin 2-dependent mechanism that inhibits the NF-κB and NLRP3 inflammasome pathways. Given its role in improving glucose tolerance and reducing chronic inflammation, FFAR4 is a promising therapeutic target for metabolic syndrome, type 2 diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD). However, drug development has been challenging due to significant species-specific differences in receptor distribution and its dualistic role in cancer, where it may promote metastasis in certain tumor environments while inhibiting growth in others.

Other names

GPR120O3FAR1PGR4GT01BMIQ10G protein-coupled receptor 120

GPR120 (FFAR4) is a Gq-coupled receptor and a beta-arrestin 2 scaffold. Activation by long-chain fatty acids or synthetic agonists stimulates GLP-1 and cholecystokinin secretion in the gut, promotes insulin-independent glucose uptake in adipocytes via GLUT4 translocation, and exerts potent anti-inflammatory effects by inhibiting NF-κB and NLRP3 inflammasome pathways through beta-arrestin 2-mediated sequestration of TAB1/TAK1 complexes.