FFAR2 Antibody
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Description
Role in Intestinal Health
FFAR2 signaling modulates gut homeostasis by regulating SCFA-mediated responses. Studies using the FFAR2 Antibody have demonstrated its expression in intestinal enteroendocrine cells (K and L cells), which secrete hormones like GLP-1 and PYY to control glucose metabolism and appetite . In Apc mutant mice (a model for colorectal cancer), FFAR2 expression correlates with polyp formation, suggesting its role in intestinal carcinogenesis .
Inflammation and Immune Response
The antibody has been used to study FFAR2's anti-inflammatory effects. Activation of FFAR2 suppresses pro-inflammatory cytokine production in neutrophils and macrophages, while promoting chemotaxis and antimicrobial peptide release . In viral infections (e.g., respiratory syncytial virus), FFAR2 agonists reduce pulmonary inflammation, as demonstrated by antibody-based knockdown experiments .
Neurological and Cancer Studies
Immunohistochemistry with the FFAR2 Antibody reveals its expression in astrocytes of mouse and rat hippocampi, linking it to neuroinflammation . In cancer research, FFAR2 is detected in various tumor cell lines (e.g., colon, breast, liver cancers), where its signaling may influence tumor growth and metastasis .
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Future Directions
Emerging research focuses on therapeutically targeting FFAR2 to address metabolic disorders, infections, and cancer. The FFAR2 Antibody is a critical tool for validating receptor expression in preclinical models and exploring its downstream signaling pathways. Ongoing studies aim to elucidate FFAR2's dual Gαq/Gαi signaling mechanisms and its interaction with the gut microbiome .
Product Specs
Buffer
Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide.
Form
Liquid
Lead Time
Typically, we can ship products within 1-3 business days after receiving your order. Delivery times may vary depending on the shipping method and destination. Please consult your local distributor for specific delivery times.
Synonyms
FFAR2; FFA2; GPCR43; GPR43; Free fatty acid receptor 2; G-protein coupled receptor 43
Target Names
Uniprot No.
Target Background
Function
FFAR2 (Free Fatty Acid Receptor 2) is a G protein-coupled receptor activated by short-chain fatty acids (SCFAs), which are major products of dietary fiber digestion. This receptor plays a crucial role in regulating whole-body energy homeostasis and intestinal immunity. In omnivorous mammals, the SCFAs acetate, propionate, and butyrate are primarily produced by the gut microbiome through the metabolism of dietary fibers. SCFAs serve not only as an energy source but also as signaling molecules.
FFAR2 is likely coupled to both the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins and the Gq family. Activation of FFAR2 leads to the generation of inositol 1,4,5-trisphosphate, mobilization of intracellular calcium, phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases, and inhibition of intracellular cAMP accumulation.
FFAR2 may contribute to glucose homeostasis by regulating the secretion of GLP-1 in response to SCFAs accumulating in the intestine. Additionally, it may regulate the production of LEP/Leptin, a hormone that acts on the central nervous system to suppress food intake. Furthermore, FFAR2 may regulate whole-body energy homeostasis through adipogenesis, influencing both the differentiation and lipid storage of adipocytes.
Alongside its role in energy homeostasis, FFAR2 may mediate the activation of inflammatory and immune responses by SCFAs in the intestine, regulating the rapid production of chemokines and cytokines. It may also play a role in resolving inflammatory responses and controlling chemotaxis in neutrophils.
In addition to SCFAs, FFAR2 can be activated by the extracellular lectin FCN1. This activation leads to the activation of monocytes and induces the secretion of interleukin-8/IL-8 in response to the presence of microbes. Among SCFAs, the fatty acids with less than 6 carbons, particularly acetate, propionate, and butyrate, are likely the most potent activators. FFAR2 exhibits a SCFA-independent constitutive G protein-coupled receptor activity.
Gene References Into Functions
- Research suggests that the free fatty acid receptor 2 (FFA2/GPR43 receptor) plays a vital role in survival during and after sepsis. PMID: 29338778
- This study demonstrates functional similarities but also significant differences between GPR84 and FFA2R in human phagocytes, providing insights into GPR84 regulation in blood neutrophils and cells recruited to an aseptic inflammatory site in vivo. PMID: 29477577
- Compared to the control group, the densitometric quantification and mean density of GPR43 and ChAT proteins, and expression of GPR43 and CHAT genes, were significantly reduced in patients with mixed refractory constipation. PMID: 26921846
- FFA2 processes are mediated by Gi signaling, whereas, in conjunction with blockade by the Gq/G11 inhibitor FR900359, the inability of AZ1729 to mimic or regulate propionate-mediated release of GLP-1 from mouse colonic preparations defined this physiological response as an endpoint transduced via activation of Gq/G11. PMID: 27385588
- The results of mutagenesis studies based on the crystal structure of hFFA1 bound to TAK-875 at 2.3 A resolution identified important residues for orthosteric agonist 6e inducing FFA2 activation. PMID: 26808470
- While both agonist and antagonist ligands contain negatively charged carboxylates that interact with two key positively charged arginine residues in transmembrane domains V and VII of FFA2, there are distinct differences in how these interactions occur. PMID: 26518871
- FFAR2 signaling occurs through divergent G protein pathways. PMID: 26075576
- GPR3 agonism potentiates insulin secretion in isolated islets. PMID: 26023106
- GPR43 expression is reduced in monocytes upon siRNA-knockdown of XBP1, while A549 cells overexpressing XBP1 displayed elevated GPR43 levels. PMID: 25633224
- FFAR2 is a potential therapeutic target for T1 diabetes, representing a link between immune response and glucose homeostasis. PMID: 25298143
- FFAR2 is expressed in pancreatic beta cells and mediates an inhibition of insulin secretion by coupling to Gi-type G proteins. PMID: 25581519
- [review] In vivo and in vitro studies suggest that short-chain fatty acid receptors (SCFAs) stimulate gut hormone secretion; therefore, the SCFA-FFA signal is likely to be important for gut physiological functions. PMID: 24458110
- GPR43 modulates NF-kappaB activity via beta-arrestin 2. PMID: 23985900
- Data indicate that a single mutation in human FFA2 of C4.57G resulted in a human FFA2 receptor with ligand selectivity similar to the bovine receptor. PMID: 22919070
- They report the results of mutagenesis studies on the receptor, and the identification of previously unknown residues that may affect receptor activation as well as residues important for allosteric interactions on FFA2. PMID: 21216233
- Reduction of GPR43 expression is associated with colon cancers. PMID: 20979106
- Collaboration among C-reactive protein, M-ficolin, and GPR43 under acidosis curtails interleukin (IL)-8 production, thus preventing immune overactivation during bacterial infection. PMID: 21037097
- Mutational analysis revealed several important residues located in transmembrane domains 3, 4, 5, 6, and 7 for acetate binding. PMID: 20837008
- Upregulation of FFAR2 expression may contribute to malignant transformation. PMID: 19780758
- FFAR2 might play a pivotal role in the differentiation and immune response of monocytes and granulocytes. PMID: 12393494
- FFA2R is expressed on leukocytes and activated by short-chain fatty acids. PMID: 12684041
- The highly selective expression of GPR43 in leukocytes, particularly polymorphonuclear cells, suggests a role in the recruitment of these cell populations toward sites of bacterial infection. PMID: 12711604
- Results indicate that the short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine L cells containing peptide YY in the human large intestine. PMID: 17899402
Database Links
Protein Families
G-protein coupled receptor 1 family
Subcellular Location
Cell membrane; Multi-pass membrane protein.
Tissue Specificity
Expressed at relatively high levels in peripheral blood leukocytes and, to lesser extent, in spleen.
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