G protein-coupled receptor 41 (GPR41), G protein-coupled receptor 43 (GPR43), and hydroxycarboxylic acid receptor 2 (HCAR2, also known as GPR109A) (GPR41, GPR43, HCAR2)

"Butyrate receptors" refer collectively to a group of metabolite-sensing cell surface proteins belonging to the **G protein-coupled receptor** family that detect the presence of the short-chain fatty acid *butyrate* along with other related molecules. The primary human proteins involved are **G protein-coupled receptor 41** (*also called* free fatty acid receptor 3 / FFAR3), **G protein-coupled receptor 43** (*free fatty acid receptor 2 / FFAR2*), and **hydroxycarboxylic acid receptor 2** (*also called* niacin/butyrate/nicotinate/salicylates-sensitive GPCR; *gene name*: HCAR2 / formerly known as *GPR109A*) [1][4]. These receptors play key roles in mediating cellular responses to gut microbiota-derived metabolites such as butyrate. They are expressed across multiple tissues—including immune cells where they regulate inflammatory responses; metabolic organs where they influence energy homeostasis; heart muscle where they can reduce contractility upon activation; neurons where they may protect against amyloid formation—and more [6][8]. Their physiological actions include dampening inflammation, promoting regulatory T-cell differentiation, controlling chemotaxis/migration of dendritic cells, regulating cardiac contractility via calcium handling mechanisms [6], influencing glucose/lipid metabolism [4], among others. Because "Butyrate Receptor" is not a unique molecular entity—but rather an umbrella term covering several distinct yet related proteins—it is important when structuring data or designing experiments/drugs/interventions that each individual gene/protein be considered separately according to its specific properties and tissue distribution [1].

Other names

Free fatty acid receptor 3 (FFAR3) for GPR41Free fatty acid receptor 2 (FFAR2) for GPR43Hydroxycarboxylic acid receptor 2 (HCAR2) or niacin receptor for GPR109AShort-chain fatty acid receptorsSCFA receptors

– Agonism at GPCRs leading to downstream signaling changes in immune cells, metabolic tissues, neurons, cardiomyocytes; typically anti-inflammatory or regulatory in nature depending on cell type activated.[1][6][8] – For HCAR2/GPR109A: Gi/o-protein coupling leads to decreased cAMP levels. – For FFAR3/GPR41 & FFAR2/GPR43: Activation modulates various intracellular pathways including cAMP reduction or phosphatidylinositol pathway activation.[6]