Free fatty acid receptor 4

Free fatty acid receptor 4

G protein-coupled receptor for long-chain fatty acids (LCFAs) with a major role in adipogenesis, energy metabolism and inflammation. Signals via G protein and beta-arrestin pathways22282525,22343897,24742677,24817122,27852822. LCFAs sensing initiates activation of phosphoinositidase C-linked G proteins GNAQ and GNA11 (G(q)/G(11)), inducing a variety of cellular responses via second messenger pathways such as intracellular calcium mobilization, modulation of cyclic adenosine monophosphate (cAMP) production, and mitogen-activated protein kinases (MAPKs)22282525,22343897,24742677,27852822. After LCFAs binding, associates with beta-arrestin ARRB2 that acts as an adapter protein coupling the receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis22282525,24817122. In response to dietary fats, plays an important role in the regulation of adipocyte proliferation and differentiation (By similarity). Acts as a receptor for omega-3 polyunsaturated fatty acids (PUFAs) at primary cilium of perivascular preadipocytes, initiating an adipogenic program via cAMP and CTCF-dependent chromatin remodeling that ultimately results in transcriptional activation of adipogenic genes and cell cycle entry (By similarity). Induces differentiation of brown adipocytes probably via autocrine and endocrine functions of FGF21 hormone (By similarity). Activates brown adipocytes by initiating intracellular calcium signaling that leads to mitochondrial depolarization and fission, and overall increased mitochondrial respiration (By similarity). Consequently stimulates fatty acid uptake and oxidation in mitochondria together with UCP1-mediated thermogenic respiration, eventually reducing fat mass (By similarity). Regulates bi-potential differentiation of bone marrow mesenchymal stem cells toward osteoblasts or adipocytes likely by up-regulating distinct integrins (By similarity). In response to dietary fats regulates hormone secretion and appetite (By similarity). Stimulates GIP and GLP1 secretion from enteroendocrine cells as well as GCG secretion in pancreatic alpha cells, thereby playing a role in the regulation of blood glucose levels (By similarity). Negatively regulates glucose-induced SST secretion in pancreatic delta cells (By similarity). Mediates LCFAs inhibition of GHRL secretion, an appetite-controlling hormone (By similarity). In taste buds, contributes to sensing of dietary fatty acids by the gustatory system (By similarity). During the inflammatory response, promotes anti-inflammatory M2 macrophage differentiation in adipose tissue (By similarity). Mediates the anti-inflammatory effects of omega-3 PUFAs via inhibition of NLRP3 inflammasome activation23809162. In this pathway, interacts with adapter protein ARRB2 and inhibits the priming step triggered by Toll-like receptors (TLRs) at the level of TAK1 and TAB1 (By similarity). Further inhibits the activation step when ARRB2 directly associates with NLRP3, leading to inhibition of pro-inflammatory cytokine release23809162. Mediates LCFAs anti-apoptotic effects (By similarity). Mediates VLCFAs-dependent liver-to-adipose tissue signaling and adipose tissue thermogenesis

Receptor for LCFAs decoupled from G protein signaling. May signal through beta-arrestin pathway. After LCFAs binding, associates with beta-arrestin ARRB2 that may act as an adapter protein coupling the receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis

Quoted from UniProt’s FUNCTION annotation for Q5NUL3 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Plasma membrane
• Vesiclesadditional
• Basal bodyadditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Cell membrane · Endosome membrane · Lysosome membrane · Cell projection, cilium membrane

Expression by cell type

Single cell type RNA, the 7 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Epicardial cells357 nCPM
• Adipocytes167 nCPM
• Goblet cells126.3 nCPM
• Somatotrophs111.5 nCPM
• Early spermatids66 nCPM
• Corticotrophs30.4 nCPM
• Microglia30 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

• intestine10.7 nTPM
• pituitary gland10.4 nTPM
• adipose tissue3.8 nTPM
• lung3.4 nTPM