SCFA receptors

Free fatty acid receptor 2 (FFAR2, GPR43) and Free fatty acid receptor 3 (FFAR3, GPR41) are the primary G protein-coupled receptors for short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. These receptors are expressed on the surface of multiple cell types—including immune cells, gut epithelial cells, and neurons—and play key roles in regulating host metabolism, energy homeostasis, hormone and neurotransmitter secretion, and immune responses. They serve as molecular mediators of gut microbiota-derived SCFA effects on both local intestinal and systemic physiology. Dysregulation or impaired signaling through these receptors has been linked to inflammatory diseases, cardiovascular disease, and neurodegenerative conditions. While termed 'SCFA receptors', this grouping encompasses several GPCRs; the most functionally and therapeutically relevant are FFAR2 and FFAR3.

Other names

FFAR2GPR43FFAR3GPR41SCFA receptorSCFARshort-chain fatty acid receptor

FFA2 and FFA3 are activated by binding SCFAs, leading to G protein-mediated intracellular signaling that impacts inflammation, metabolism, and hormone secretion. Activation of FFA2/FFA3 results in modulation of cyclic AMP, calcium signaling, and downstream cytokine release.