Historical Background
GPR41 (also known as free fatty acid receptor 3 or FFAR3) was identified as a G protein-coupled receptors (GPCRs) in 1997 (Sawzdargo et al. 1997). Sawzdargo et al. discovered GPR40–43, which were identified as tandemly encoded genes present on human chromosomal locus 19q13.1. Human GPR41 (hGPR41) had the same nucleotide length as human GPR42 (hGPR42) and differed by only six amino acids (Sawzdargo et al. 1997). Brown et al. performed similarity searches using public sequence databases to find mammalian orthologues of the hGPR41/hGPR42 pair. They found the mouse locus, which was syntenic with human 19q13.1, contained GPR40–43 orthologues. Only one orthologue of the hGPR41/hGPR42 pair was detected (72% amino acid similarity to hGPR41) (Brown et al. 2003). They also identified bovine and rat orthologues from the overlapping sequences. The amino acid sequences of the orthologues...
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ahrén IL, Xu J, Önning G, Olsson C, Ahrné S, Molin G. Antihypertensive activity of blueberries fermented by Lactobacillus plantarum DSM 15313 and effects on the gut microbiota in healthy rats. Clin Nutr. 2015;34:719–26.
Bellahcene M, O’Dowd JF, Wargent ET, Zaibi MS, Hislop DC, Ngala RA, Smith DM, Cawthorne MA, Stocker CJ, Arch JR. Male mice that lack the G-protein-coupled receptor GPR41 have low energy expenditure and increased body fat content. Br J Nutr. 2013;109:1755–64.
Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ, Pike NB, Strum JC, Steplewski KM, Murdock PR, Holder JC, Marshall FH, Szekeres PG, Wilson S, Ignar DM, Foord SM, Wise A, Dowell SJ. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem. 2003;278:11312–9.
De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Bäckhed F, Mithieux G. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156:84–96.
Donohoe DR, Garge N, Zhang X, Sun W, O’Connell TM, Bunger MK, Bultman SJ. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011;13:517–26.
Hudson BD, Christiansen E, Murdoch H, Jenkins L, Hansen AH, Madsen O, Ulven T, Milligan G. Complex pharmacology of novel allosteric free fatty acid 3 receptor ligands. Mol Pharmacol. 2014;86:200–10.
Inoue D, Kimura I, Wakabayashi M, Tsumoto H, Ozawa K, Hara T, Takei Y, Hirasawa A, Ishihama Y, Tsujimoto G. Short-chain fatty acid receptor GPR41-mediated activation of sympathetic neurons involves synapsin 2b phosphorylation. FEBS Lett. 2012;586:1547–54.
Pluznick J. A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes. 2014;5:202–7.
Kim MH, Kang SG, Park JH, Yanagisawa M, Kim CH. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology. 2013;145:396–406.
Kimura I, Inoue D, Maeda T, Hara T, Ichimura A, Miyauchi S, Kobayashi M, Hirasawa A, Tsujimoto G. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci USA. 2011;108:8030–5.
Le Poul E, Loison C, Struyf S, Springael JY, Lannoy V, Decobecq ME, Brezillon S, Dupriez V, Vassart G, Van Damme J, Parmentier M, Detheux M. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem. 2003;278:25481–9.
Leonard JN, Chu ZL, Bruce MA, Boatman PD. Gpr41 and modulators thereof for the treatment of insulin-related disorders. WO Patent. 2006;06052566.
Lye HS, Kuan CY, Ewe JA, Fung WY, Liong MT. The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens. Int J Mol Sci. 2009;10:3755–75.
Nøhr MK, Pedersen MH, Gille A, Egerod KL, Engelstoft MS, Husted AS, Sichlau RM, Grunddal KV, Poulsen SS, Han S, Jones RM, Offermanns S, Schwartz TW. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology. 2013;154:3552–64.
Offermanns S. Free fatty acid (FFA) and hydroxy carboxylic acid (HCA) receptors. Annu Rev Pharmacol Toxicol. 2014;54:407–34.
Pivovarova O, Hornemann S, Weimer S, Lu Y, Murahovschi V, Zhuk S, Seltmann AC, Malashicheva A, Kostareva A, Kruse M, Busjahn A, Rudovich N, Pfeiffer AF. Regulation of nutrition-associated receptors in blood monocytes of normal weight and obese humans. Peptides. 2015;65:12–9.
Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, Brunet I, Wan LX, Rey F, Wang T, Firestein SJ, Yanagisawa M, Gordon JI, Eichmann A, Peti-Peterdi J, Caplan MJ. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci U S A. 2013;110:4410–5.
Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA. 2008;105:16767–72.
Sawzdargo M, George SR, Nguyen T, Xu S, Kolakowski LF, O'Dowd BF. A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1. Biochem Biophys Res Commun. 1997;239:543–7.
Tang C, Ahmed K, Gille A, Lu S, Gröne HJ, Tunaru S, Offermanns S. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat Med. 2015;21:173–7.
Tazoe H, Otomo Y, Karaki S, Kato I, Fukami Y, Terasaki M, Kuwahara A. Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed Res. 2009;30:149–56.
Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61:364–71.
Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev. 2001;81:1031–64.
Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, Blanchard C, Junt T, Nicod LP, Harris NL, Marsland BJ. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med. 2014;20:159–66.
Xiong Y, Miyamoto N, Shibata K, Valasek MA, Motoike T, Kedzierski RM, Yanagisawa M. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci U S A. 2004;101:1045–50.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Nakajima, A., Kimura, I. (2018). GPR41/FFAR3. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101609
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101609
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences