FFAR2

This gene encodes a member of the GP40 family of G protein-coupled receptors that are clustered together on chromosome 19. The encoded protein is a receptor for short chain free fatty acids and may be involved in the inflammatory response and in regulating lipid plasma levels. [provided by RefSeq, Apr 2009]

Full Name

Free Fatty Acid Receptor 2

Research Area

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).

Biological Process

Cell surface pattern recognition receptor signaling pathway Source: UniProtKB
Cellular response to fatty acid Source: UniProtKB
Fat cell differentiation Source: UniProtKB
Glucose homeostasis Source: UniProtKB
G protein-coupled receptor signaling pathway Source: UniProtKB
Leukocyte chemotaxis involved in inflammatory response Source: UniProtKB
Lipid storage Source: UniProtKB
Mucosal immune response Source: UniProtKB
Positive regulation of acute inflammatory response to non-antigenic stimulus Source: UniProtKB
Positive regulation of chemokine production Source: UniProtKB
Positive regulation of cytokine production involved in immune response Source: UniProtKB
Positive regulation of interleukin-8 production Source: UniProtKB
Regulation of acute inflammatory response Source: UniProtKB
Regulation of peptide hormone secretion Source: UniProtKB

Cellular Location

Cell membrane

Topology

Extracellular: 1-12
Helical: 13-33
Cytoplasmic: 34-41
Helical: 42-62
Extracellular: 63-84
Helical: 85-105
Cytoplasmic: 106-126
Helical: 127-147
Extracellular: 148-173
Helical: 174-194
Cytoplasmic: 195-219
Helical: 220-240
Extracellular: 241-255
Helical: 256-276
Cytoplasmic: 277-330