Free fatty acid receptor 3 information

FFAR3
Identifiers
Aliases	FFAR3, FFA3R, GPR41, GPR42, free fatty acid receptor 3
External IDs	OMIM: 603821 MGI: 2685324 HomoloGene: 82482 GeneCards: FFAR3
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.12 Start 35,358,460 bp[1] End 35,360,489 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B1 Start 30,553,755 bp[2] End 30,555,603 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood islet of Langerhans appendix subcutaneous adipose tissue monocyte gallbladder smooth muscle tissue spleen fundus duodenum Top expressed in islet of Langerhans proximal tubule autonomic nervous system sympathetic nervous system blastocyst sympathetic ganglion duodenum colon ileum jejunum More reference expression data BioGPS n/a
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity lipid binding Cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane Biological process mucosal immune response regulation of norepinephrine secretion adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway negative regulation of blood pressure immune system process positive regulation of cytokine production involved in immune response regulation of hormone biosynthetic process cellular response to fatty acid positive regulation of acute inflammatory response to non-antigenic stimulus positive regulation of chemokine production inflammatory response regulation of peptide hormone secretion signal transduction G protein-coupled receptor signaling pathway regulation of insulin receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2865 233080 Ensembl ENSG00000185897 ENSMUSG00000019429 UniProt O14843 Q3UFD7 RefSeq (mRNA) NM_005304 NM_001033316 RefSeq (protein) NP_005295 NP_001028488 Location (UCSC) Chr 19: 35.36 – 35.36 Mb Chr 7: 30.55 – 30.56 Mb PubMed search [3] [4]
Wikidata
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Free fatty acid receptor 3 (FFAR3, also termed GPR41) protein is a G protein coupled receptor (i.e., GPR or GPCR) that in humans is encoded by the FFAR3 gene (i.e., GPR41 gene).^[5] GPRs reside on cell surfaces, bind specific signaling molecules, and thereby are activated to trigger certain functional responses in their parent cells. FFAR3 is a member of the free fatty acid receptor group of GPRs that includes FFAR1 (i.e., GPR40), FFAR2 (i.e., GPR43), and FFAR4 (i.e., GPR120).^[6] All of these FFARs are activated by fatty acids. FFAR3 and FFAR2 are activated by certain short-chain fatty acids (SC-FAs), i.e., fatty acids consisting of 2 to 6 carbon atoms^[7] whereas FFFAR1 and FFAR4 are activated by certain fatty acids that are 6 to more than 21 carbon atoms long.^[8][9][10] Hydroxycarboxylic acid receptor 2 is also activated by a SC-FA that activate FFAR3, i.e., butyric acid.^[11]

The human FFAR3 gene is located next to the FFAR2 gene at locus 13.12 on the long (i.e., "q") arm of chromosome 19 (location abbreviated as 19q13.12). The human FFAR3 and FFAR2 proteins consist of 346 and 330 amino acids, respectively,^[12] and share about a 40% amino acid sequence homology.^[13] The two FFARs have been found to form a heteromer complex (i.e., FFAR3 and FFAR2 bind to each other and are activated together by a SC-FA) in human monocytes, macrophages, and the immortalized embryonic kidney cells, HEK 293 cells. When stimulated by a SC-FA, the cells expressing both FFAR3 and FFAR2 may form this heterodimer and thereby activate cell signaling pathways and mount responses that differ from those of cells expressing only one of these FFARs.^[14] The formation of GPR43-GPR41 heterodimers has not been evaluated in most studies and may explain otherwise conflicting results on the roles of FFAR3 and FFAR2 in cell function.^[10][15][16] Furthermore, SC-FAs can alter the function of cells independently of FFAR3 and FFAR2 by altering the activity of cellular histone deacetylases which regulate the transcription of various genes or by altering metabolic pathways which alter cell functions.^[17][18] Given these alternate ways for SC-FAs to activate cells as wells at the ability of SC-FAs to activate FFAR2 or, in the case of butyric acid, hydroxycarboxylic acid receptor 2, the studies reported here focus on those showing that the examined action(s) of an SC-FA is absent or reduced in cells, tissues, or animals that have no or reduced FFAR3 activity due respectively to knockout (i.e., removal or inactivation) or knockdown (i.e., reduction) of the FFAR3 protein gene, i.e., the Ffar3 gene in animals or FFAR3 gene in humans.

Certain bacteria in the gastrointestinal tract ferment fecal fiber into SC-FAs and excrete them as waste products. The excreted SC-FAs enter the gastrointestinal walls, diffuse into the portal venous system, and ultimately flow into the systemic circulation. During this passage, they can activate the FFAR3 on cells in the intestinal wall as well as throughout the body.^[19] This activation may: suppress the appetite for food and thereby reduce overeating and the development of obesity;^[20][21] inhibit the liver's accumulation of fatty acids and thereby the development of fatty liver diseases;^[22] decrease blood pressure and thereby the development of hypertension and hypertension-related cardiac diseases;^[23] modulate insulin secretion and thereby the development and/or symptoms of type 2 diabetes;^[24] reduce heart rate and blood plasma norepinephrine levels and thereby lower total body energy expenditures;^[19] and suppress or delay the development of allergic asthma.^[25]

The specific types of bacteria in the intestines can be modified to increase the number which make SC-FAs by using foods that stimulate the growth of these bacteria (i.e., prebiotics), preparations of SC-FA-producing bacteria (i.e., probiotics), or both methods (see synbiotics).^[26] Individuals with disorders that are associated with low levels of the SC-FA-producing intestinal bacteria may show improvements in their conditions when treated with prebiotics, probiotics, or synbiotics while individuals with disorders associated with high levels of SC-FAs may show improvements in their conditions when treated with methods, e.g., antibiotics, that reduce the intestinal levels of these bacteria.^[19][27] (For information on these treatments see Disorders treated by probiotics and Disorders treated by prebiotics). In addition, drugs are being tested for their ability to act more usefully, potently, and effectively than SC-FAs in stimulating or inhibiting FFAR3 and thereby for treating the disoders that are inhibited or stimulated, respectively, by SC-FAs.^[28]