FFAR2

Description

The FFAR2 (free fatty acid receptor 2) is a protein-coding gene located on chromosome 19.

Free fatty acid receptor 2 (FFAR2), also known as G-protein coupled receptor 43 (GPR43), is a rhodopsin-like G-protein coupled receptor (GPCR) encoded by the FFAR2 gene. In humans, the FFAR2 gene is located on the long arm of chromosome 19 at position 13.12 (19q13.12). FFAR2, like other GPCRs, is located on the cell membrane and is activated by binding specific ligands, regulating various cellular functions. FFAR2 is part of the free fatty acid receptor family, which also includes FFAR1 (GPR40), FFAR3 (GPR41), and FFAR4 (GPR120). FFAR2 and FFAR3 are activated by short-chain fatty acids (SCFAs), while FFAR1 and FFAR4 respond to long-chain fatty acids. SCFAs, produced by intestinal bacteria, play a key role in various bodily functions by activating FFAR2. This receptor is implicated in regulating insulin and glucose levels, inflammation, fat tissue development, and certain cancerous and non-cancerous cell growth. Due to its role in these processes, FFAR2 has been studied for its potential involvement in conditions such as diabetes, inflammation, obesity, ketoacidosis, certain types of cancer, neurological diseases, and infections. Therapies targeting FFAR2 are being developed to modulate its activity in these conditions, offering potential new treatments for diseases influenced by SCFAs.

== Activators and inhibitors == FFAR2 and FFR3 are activated primarily by short-chain fatty acids (SCFAs) that are 2 to 6 carbons in length (see length of fatty acids).

G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins but also to the Gq family (PubMed:12496283, PubMed:12711604, PubMed:23589301). Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. May play a role in glucose homeostasis by regulating the secretion of GLP-1, in response to short-chain fatty acids accumulating in the intestine. May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake. Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes. In parallel to its role in energy homeostasis, may also mediate the activation of the inflammatory and immune responses by SCFA in the intestine, regulating the rapid production of chemokines and cytokines. May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils. In addition to SCFAs, may also be activated by the extracellular lectin FCN1 in a process leading to activation of monocytes and inducing the secretion of interleukin-8/IL-8 in response to the presence of microbes (PubMed:21037097). Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably acetate, propionate and butyrate (PubMed:12496283, PubMed:12711604). Exhibits a SCFA- independent constitutive G protein-coupled receptor activity (PubMed:23066016). {ECO:0000269|PubMed:12496283, ECO:0000269|PubMed:12684041, ECO:0000269|PubMed:12711604, ECO:0000269|PubMed:18801738, ECO:0000269|PubMed:21037097, ECO:0000269|PubMed:23066016, ECO:0000269|PubMed:23589301}

FFAR2 is also known as FFA2R, GPR43.

Associated Diseases

WES Whole Exome Sequencing