Free fatty acid receptor 2 (GPR43) (FFAR2)

Free fatty acid receptor 2 (FFAR2), also known as GPR43, is a G protein-coupled receptor that serves as a primary sensor for short-chain fatty acids (SCFAs) such as acetate and propionate, which are metabolic byproducts of gut microbiota fermentation (UniProt P41145). FFAR2 is predominantly expressed on immune cells, including neutrophils and mast cells, where it acts as a critical link between microbial metabolism and the host immune system (Tan et al., 2014). Activation of FFAR2 by SCFAs has been shown to suppress mast cell degranulation and the subsequent release of inflammatory mediators like histamine and cytokines, thereby playing a protective role in allergic and inflammatory conditions (Folkerts et al., 2020). This receptor modulates intracellular signaling through Gi and Gq proteins, influencing chemotaxis and the production of reactive oxygen species. In disease contexts, the dysregulation of the SCFA-FFAR2 axis is associated with asthma, food allergies, and inflammatory bowel disease, making it a target of interest for therapeutic intervention. Drugs targeting FFAR2, including small molecule agonists and antagonists, are being explored for their potential to treat these immune-mediated disorders by restoring homeostatic immune signaling.

Other names

G-protein coupled receptor 43GPR43FFA2RFree fatty acid receptor 2

Agonism of the receptor by short-chain fatty acids (SCFAs) leads to the activation of Gi and Gq signaling pathways, which modulates immune cell activity and inhibits the release of pro-inflammatory mediators from mast cells.