Free fatty acid receptor 2 (FFAR2), Free fatty acid receptor 3 (FFAR3), and Hydroxycarboxylic acid receptor 2 (HCAR2) (FFAR2, FFAR3, HCAR2)

This target group comprises three distinct G protein-coupled receptors—Free Fatty Acid Receptor 2 (FFAR2/GPR43), Free Fatty Acid Receptor 3 (FFAR3/GPR41), and Hydroxycarboxylic Acid Receptor 2 (HCAR2/GPR109A)—which serve as primary sensors for short-chain fatty acids (SCFAs) produced by gut microbiota fermentation (Brown et al., 2003, PMID: 12531899). FFAR2 and FFAR3 are activated by acetate, propionate, and butyrate, playing critical roles in regulating immune cell chemotaxis, metabolic hormone secretion (such as GLP-1 and PYY), and energy homeostasis (Priyadarshini et al., 2016, PMID: 26829168). HCAR2, while primarily known as a high-affinity receptor for niacin, also responds to the SCFA butyrate and mediates anti-inflammatory effects in the colon and adipose tissue (Thangaraju et al., 2009, PMID: 19244115). Together, these receptors link the gut microbiome to host physiology, influencing conditions such as inflammatory bowel disease, obesity, and cardiovascular health (Tan et al., 2014, PMID: 24782830). Therapeutic strategies targeting these receptors aim to modulate metabolic and inflammatory pathways, though challenges include achieving receptor selectivity and managing systemic side effects like niacin-induced flushing (Offermanns, 2014, PMID: 24663265).

Other names

GPR43GPR41GPR109ANIACR1Free fatty acid receptor 2Free fatty acid receptor 3Hydroxycarboxylic acid receptor 2Nicotinic acid receptorG-protein coupled receptor 43G-protein coupled receptor 41G-protein coupled receptor 109A

Agonism of Gi/o and Gq protein-coupled signaling pathways to modulate intracellular cAMP levels and calcium mobilization (Brown et al., 2003; Offermanns, 2014).