Free fatty acid receptor 3 (FFA3) (FFA3)

Free fatty acid receptor 3 (FFA3), also known as GPR41, is a G protein-coupled receptor that serves as a primary sensor for short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate, which are produced by the gut microbiota during the fermentation of dietary fiber. It is predominantly expressed in enteroendocrine cells, sympathetic ganglia, and pancreatic beta-cells, playing a vital role in linking gut microbial activity to host metabolic and physiological processes. Upon activation, FFA3 primarily couples with Gi/o proteins to inhibit cAMP production and stimulate the ERK1/2 pathway, leading to the secretion of satiety hormones like peptide YY (PYY) and glucagon-like peptide-1 (GLP-1). These actions contribute to the regulation of energy homeostasis, glucose metabolism, and immune responses, making FFA3 a significant therapeutic target for metabolic diseases such as obesity and type 2 diabetes, as well as inflammatory conditions. In addition to metabolic roles, FFA3 is involved in immune modulation and has been implicated in inflammatory diseases such as asthma and colitis. Its expression in the sympathetic nervous system suggests a role in regulating blood pressure and heart rate, further expanding its potential as a target for cardiovascular health. Despite its promise, the lack of highly selective small-molecule ligands has historically hindered the clinical translation of FFA3-targeted therapies.

Other names

GPR41G-protein coupled receptor 41FFAR3FFA3RLSSIG

Agonism of the Gi/o-coupled receptor, which inhibits adenylate cyclase to decrease intracellular cAMP levels, activates the mitogen-activated protein kinase (MAPK) pathway (specifically ERK1/2), and triggers intracellular calcium mobilization.