Free fatty acids-sensing g protein-coupled receptors in drug targeting and therapeutics

Current Medicinal Chemistry

Volumn 20, Issue 31, 2013, Pages 3855-3871

  Yonezawa, Tomo ^a,b,c   Kurata, Riho ^d,e   Yoshida, Kaori ^e   Murayama, Masanori A ^e   Cui, Xiaofeng ^a   Hasegawa, Akihiko ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^c TOKYO UNIVERSITY OF SCIENCE   (Japan)

^d TOKAI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^e UNIVERSITY OF TOKYO   (Japan)

Author keywords

Free fatty acids; GPR120; GPR40; GPR41; GPR43; GPR84

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; 3,3,14,14 TETRAMETHYLHEXADECANEDIOIC ACID; ANTIDIABETIC AGENT; CHOLECYSTOKININ; ESN 280; ESN 282; FASIGLIFAM; FATTY ACID; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 120; G PROTEIN COUPLED RECEPTOR 40; G PROTEIN COUPLED RECEPTOR 41; G PROTEIN COUPLED RECEPTOR 43; G PROTEIN COUPLED RECEPTOR 84; GALANIN RECEPTOR; GLUCAGON LIKE PEPTIDE 1; GW 9508; INSULIN; LONG CHAIN FATTY ACID; MEMBRANE PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NETOGLITAZONE; PERTUSSIS TOXIN; PROTEIN KINASE B; ROSIGLITAZONE; SHORT CHAIN FATTY ACID; SYNTHETIC PEPTIDE; TRANSIENT RECEPTOR POTENTIAL CHANNEL M5; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADIPOCYTE; ADIPOGENESIS; ADIPOSE TISSUE; ARTICLE; ASTROCYTE; BRAIN; BREAST CANCER; CANCER CELL; CELL PROLIFERATION; CHEMOTAXIS; CHROMOSOME 19Q; CHROMOSOME 19Q13; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; DRUG TARGETING; ENTEROENDOCRINE CELL; EXPRESSED SEQUENCE TAG; GENE TARGETING; HUMAN; IMMUNOCOMPETENT CELL; IN VIVO STUDY; INSULIN RELEASE; INTESTINE; LEUKOCYTE; MONOCYTE MACROPHAGE PRECURSOR CELL; NERVE CELL; NERVE CELL DIFFERENTIATION; NONHUMAN; PANCREAS; PANCREAS ISLET BETA CELL; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TASTE BUD; WESTERN BLOTTING;

ADIPOSE TISSUE; ANIMALS; BRAIN; BREAST NEOPLASMS; DRUG THERAPY; FATTY ACIDS, NONESTERIFIED; FEMALE; GENE TARGETING; HUMANS; INTESTINES; RECEPTORS, G-PROTEIN-COUPLED; TASTE BUDS;

EID: 84887892433     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/09298673113209990168     Document Type: Article

References (129)

1. Dekker, L.V.; Parker, P.J. Protein kinase C-a question of specificity. Trends. Biochem. Sci., 1994, 19, 73-77.
2. Cummings, J.H.; Macfarlane, G.T. Role of intestinal bacteria in nutrient metabolism. JPEN J. Parenter. Enteral. Nutr., 1997, 21, 357-365.
3. Mortensen, P.B.; Clausen, M.R. Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand. J. Gastroenterol., 1996, 216, 132-148.
4. von Engelhardt, W.; Bartels, J.; Kirschberger, S.; Meyer zu Duttingdorf, H.D.; Busche, R. Role of short-chain fatty acids in the hind gut. Vet. Q., 1998, 20, S52-59.
5. Bergman, E.N., Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol. Rev., 1990, 70, 567-590.
6. Wolever, T.M.; Josse, R.G.; Leiter, L.A.; Chiasson, J.L. Time of day and glucose tolerance status affect serum short-chain fatty acid concentrations in humans. Metabolism, 1997, 46, 805-811.
7. Bergman, J.; Kamien, J.B.; Spealman, R.D. Antagonism of cocaine self-administration by selective dopamine D(1) and D(2) antagonists. Behav. Pharmacol., 1990, 1, 355-363.
8. Siler, S.Q.; Neese, R.A.; Hellerstein, M.K. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am. J. Clin. Nutr., 1999, 70, 928-936.
9. Matsunaga, N.; Kubota, I.; Roh, S.G.; He, M.L.; Hidaka, S.; Hidari, H.; Sasaki, Y. Effect of mesenteric venous volatile fatty acids (VFA) infusion on GH secretion in sheep. Endocr. J., 1997, 44, 707-714.
10. Annison, E.F.; Bicherstaffe, R.; Linzell, J.L. Glucose and fatty acid metabolism in cows roducing milk of low fat content. J. Agric. Sci. Camb., 1974, 82, 87-95.
11. Linzell, J.L.; Annison, E.F.; Bickerstaffe, R.; Jeffcott, L.B. Mammary and whole-body metabolism of glucose, acetate and plamitate in the lactating horse. Proc. Nutr. Soc., 1972, 31, 72A-73A
12. Eftimiadi, C.; Buzzi, E.; Tonetti, M.; Buffa, P.; Buffa, D.; van Steenbergen, M.T.; de Graaff, J.; Botta, G.A. Short-chain fatty acids produced by anaerobic bacteria alter the physiological responses of human neutrophils to chemotactic peptide. J. Infect., 1987, 14, 43-53.
13. Brunkhorst, B.A.; Kraus, E.; Coppi, M.; Budnick, M.; Niederman, R. Propionate induces polymorphonuclear leukocyte activation and inhibits formylmethionyl-leucyl-phenylalanine-stimulated activation. Infect. Immun., 1992, 60, 2957-2968.
14. Nakao, S.; Fujii, A.; Niederman, R. Alteration of cytoplasmic Ca2+ in resting and stimulated human neutrophils by short-chain carboxylic acids at neutral pH. Infect. Immun., 1992, 60, 5307-5311.
15. Stehle, H.W.; Leblebicioglu, B.; Walters, J.D. Short-chain carboxylic acids produced by gram-negative anaerobic bacteria can accelerate or delay polymorphonuclear leukocyte apoptosis in vitro. J. Periodontol., 2001, 72, 1059-1063.
16. Papamandjaris, A.A.; MacDougall, D.E.; Jones, P.J. Medium chain fatty acid metabolism and energy expenditure: obesity treatment implications. Life Sci., 1998, 62, 1203-1215.
17. Chawla, A.; Repa, J.J.; Evans, R.M.; Mangelsdorf, D.J. Nuclear receptors and lipid physiology: opening the X-files. Science 2001, 294, 1866-1870.
18. Angulo, P. Obesity and nonalcoholic fatty liver disease. Nutr. Rev., 2007, 65, S57-63.
19. Guardado-Mendoza, R.; Davalli, A.M.; Chavez, A.O.; Hubbard, G.B.; Dick, E.J.; Majluf-Cruz, A.; Tene-Perez, C.E.; Goldschmidt, L.; Hart, J.; Perego, C.; Comuzzie, A.G.; Tejero, M.E.; Finzi, G.; Placidi, C.; La Rosa, S.; Capella, C.; Halff, G.; Gastaldelli, A.; DeFronzo, R.A.; Folli, F. Pancreatic islet amyloidosis, beta-cell apoptosis, and alpha-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons. Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 13992-13997.
20. Musa-Veloso, K.; Binns, M.A.; Kocenas, A.; Chung, C.; Rice, H.; Oppedal-Olsen, H.; Lloyd, H.; Lemke, S. Impact of low v. moderate intakes of long-chain n-3 fatty acids on risk of coronary heartdisease. Br. J. Nutr., 2011, 106, 1129-1141.
21. Wang, L.; Folsom, A.R.; Zheng, Z.J.; Pankow, J.S.; Eckfeldt, J.H. ARIC Study Investigators. Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am. J. Clin. Nutr., 2003, 78, 91-98.
22. Chavez, A.O.; Gastaldelli, A.; Guardado-Mendoza, R.; Lopez-Alvarenga, J.C.; Leland, M.M.; Tejero, M.E.; Sorice, G.; Casiraghi, F.; Davalli, A.; Bastarrachea, R.A.; Comuzzie, A.G.; DeFronzo, R.A.; Folli, F. Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons. Cardiovasc. Diabetol., 2009, 8, 22.
23. Gong, D.W.; He, Y.; Karas, M.; Reitman, M. Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. J. Biol. Chem., 1997, 272, 24129-24132.
24. Fleury, C.; Neverova, M.; Collins, S.; Raimbault, S.; Champigny, O.; Levi-Meyrueis, C.; Bouillaud, F.; Seldin, M.F.; Surwit, R.S.; Ricquier, D.; Warden, C.H. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat. Genet., 1997, 15, 269-272.
25. Brun, S.; Carmona, M.C.; Mampel, T.; Viñas, O.; Giralt, M.; Iglesias, R.; Villarroya, F. Activators of peroxisome proliferator-activated receptor-alpha induce the expression of the uncoupling protein-3 gene in skeletal muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth. Diabetes. 1999, 48, 1217-1222.
26. Faggioni, R.; Shigenaga, J.; Moser, A.; Feingold, K.R.; Grunfeld, C. Induction of UCP2 gene expression by LPS: a potential mechanism for increased thermogenesis during infection. Biochem. Biophys. Res. Commun., 1998, 244, 75-78.
27. Kageyama, H.; Suga, A.; Kashiba, M.; Oka, J.; Osaka, T.; Kashiwa, T.; Hirano, T.; Nemoto, K.; Namba, Y., Ricquier, D., Giacobino, J.P., and Inoue, S. Increased uncoupling protein-2 and-3 gene expressions in skeletal muscle of STZ-induced diabetic rats. FEBS Lett., 1998, 440, 450-453.
28. Itoh, Y.; Kawamata, Y.; Harada, M.; Kobayashi, M.; Fujii, R.; Fukusumi, S.; Ogi, K., Hosoya, M.; Tanaka, Y.; Uejima, H.; Tanaka, H.; Maruyama, M.; Satoh, R.; Okubo, S.; Kizawa, H.; Komatsu, H.; Matsumura, F.; Noguchi, Y.; Shinohara, T.; Hinuma, S.; Fujisawa, Y.; Fujino, M. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature. 2003, 422, 173-176.
29. Briscoe, C.P.; Tadayyon, M.; Andrews, J.L.; Benson, W.G.; Chambers, J.K.; Eilert, M.M.; Ellis, C.; Elshourbagy, N.A.; Goetz, A.S.; Minnick, D.T.; Murdock, P.R.; Sauls, H.R. Jr, Shabon, U.; Spinage, L.D.; Strum, J.C.; Szekeres, P.G.; Tan, K.B.; Way, J.M.; Ignar, D.M.; Wilson, S.; Muir, A.I. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J. Biol. Chem., 2003, 278, 11303-11311.
30. Kotarsky, K.; Nilsson, N.E.; Flodgren, E.; Owman, C.; Olde, B. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs. Biochem. Biophys. Res. Commun., 2003, 301, 406-410.
31. Hirasawa, A.; Tsumaya, K.; Awaji, T.; Katsuma, S.; Adachi, T.; Yamada, M.; Sugimoto, Y.; Miyazaki, S.; Tsujimoto, G. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat. Med., 2005, 11, 90-94.
32. Wang, J.; Wu, X.; Simonavicius, N.; Tian, H.; Ling, L. Mediumchain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J. Biol. Chem., 2006, 281, 34457-34464.
33. Brown, A.J.; Goldsworthy, S.M.; Barnes, A.A.; Eilert, M.M.; Tcheang, L.; Daniels, D.; Muir, A.I.; Wigglesworth, M.J.; Kinghorn, I.; Fraser, N.J.; Pike, N.B.; Strum, J.C.; Steplewski, K.M.; Murdock, P.R.; Holder, J.C.; Marshall, F.H.; Szekeres, P.G.; Wilson, S.; Ignar, D.M.; Foord, S.M.; Wise, A.; Dowell, S.J. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem., 2003, 278, 11312-11319.
34. Nilsson, N.E.; Kotarsky, K.; Owman, C.; Olde, B. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem. Biophys. Res. Commun., 2003, 303, 1047-1052.
35. Le Poul, E.; Loison, C.; Struyf, S.; Springael, J.Y.; Lannoy, V.; Decobecq, M.E.; 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, 25481-25489.
36. Gasperi, V.; Dainese, E.; Oddi, S.; Sabatucci, A.; Maccarrone, M. GPR55and its Interaction with Membrane Lipids: Comparison with OtherEndocannabinoid-Binding Receptors. Curr. Med. Chem., 2013, 20, 64-78.
37. Jafurulla, Md.; Chattopadhyay, A. Membrane Lipids in the Function of Serotonin and Adrenergic Receptors. Curr. Med. Chem., 2013, 20, 47-55.
38. Sawzdargo, M.; George, S.R.; Nguyen, T.; Xu, S.; Kolakowski, L.F.; O'Dowd, B.F. A cluster of four novel human G proteincoupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1. Biochem. Biophys. Res. Commun., 1997, 239, 543-7.
39. Roduit, R.; Nolan, C.; Alarcon, C.; Moore, P.; Barbeau, A.; Delghingaro-Augusto, V.; Przybykowski, E.; Morin, J.; Masse, F.; Massie, B.; Ruderman, N.; Rhodes, C.; Poitout, V.; Prentki, M. A role for the malonyl-CoA/long-chain acyl-CoA pathway of lipid signaling in the regulation of insulin secretion in response to both fuel and nonfuel stimuli. Diabetes, 2004, 53, 1007-1019
40. Fredriksson, R.; Höglund, P.J.; Gloriam, D.E.; Lagerström, M.C.; Schiöth, H.B. Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives. FEBS Lett., 2003, 554, 381-388.
41. Katsuma, S.; Hatae, N.; Yano, T.; Ruike, Y.; Kimura, M.; Hirasawa, A.; Tsujimoto, G. Free fatty acids inhibit serum deprivation-induced apoptosis through GPR120 in a murine enteroendocrine cell line STC-1. J. Biol. Chem., 2005, 280, 19507-19515.
42. French, S.J.; Conlon, C.A.; Mutuma, S.T.; Arnold, M.; Read, N.W.; Meijer, G.; Francis, J. The effects of intestinal infusion of long-chain fatty acids on food intake in humans. Gastroenterology, 2000, 119, 943-948.
43. McLaughlin, J.; Grazia Lucà, M.; Jones, M.N.; D'Amato, M.; Dockray, G.J.; Thompson, D.G. Fatty acid chain length determines cholecystokinin secretion and effect on human gastric motility. Gastroenterology, 1999, 116, 46-53.
44. Tanaka, T.; Katsuma, S.; Adachi, T.; Koshimizu, T.A.; Hirasawa, A.; Tsujimoto, G. Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn. Schmiedebergs Arch. Pharmacol., 2008 Jun, 377(4-6), 523-7.
45. Parker, H.E.; Habib, A.M.; Rogers, G.J.; Gribble, F.M.; Reimann, F. Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells. Diabetologia, 2009, 52, 289-298.
46. Hirasawa, A.; Hara, T.; Katsuma, S.; Adachi, T.; Tsujimoto, G. Free fatty acid receptors and drug discovery. Biol. Pharm. Bull., 2008, 31, 1847-1851.
47. Yonezawa, T.; Katoh, K.; Obara, Y. Existence of GPR40 functioning in a human breast cancer cell line, MCF-7. Biochem. Biophys. Res. Commun. 2004, 314, 805-809.
48. Yonezawa, T.; Haga, S.; Kobayashi, Y.; Katoh, K.; Obara, Y. Unsaturated fatty acids promote proliferation via ERK1/2 and Akt pathway in bovinemammary epithelial cells. Biochem. Biophys. Res. Commun., 2008, 367, 729-735.
49. Hardy, S.; St-Onge, G.G.; Joly, E.; Langelier, Y.; Prentki, M. Oleate promotes the proliferation of breast cancer cells via the G protein-coupled receptor GPR40. J. Biol. Chem., 2005, 280, 13285-13291.
50. Soto-Guzman, A.; Robledo, T.; Lopez-Perez, M.; Salazar, E.P. Oleic acid induces ERK1/2 activation and AP-1 DNA binding activity through a mechanism involving Src kinase and EGFR transactivation in breast cancer cells. Mol. Cell. Endocrinol., 2008, 294, 81-91.
51. Cartoni C, Yasumatsu K, Ohkuri T, Shigemura N, Yoshida R, Godinot N, le Coutre J, Ninomiya Y, Damak S. Taste preference for fatty acids is mediated by GPR40 and GPR120. J Neurosci., 2010 Jun 23, 30(25):8376-8382.
52. Galindo, M.M.; Voigt, N.; Stein, J.; van Lengerich, J.; Raguse, J.D.; Hofmann, T.; Meyerhof, W.; Behrens, M. G protein-coupled receptors in human fat taste perception. Chem. Senses., 2012, 37, 123-139.
53. Matsumura, S.; Mizushige, T.; Yoneda, T.; Iwanaga, T.; Tsuzuki, S.; Inoue, K.; Fushiki, T. GPR expression in the rat taste bud relating to fatty acid sensing. Biomed. Res., 2007, 28, 49-55.
54. Matsumura, S.; Eguchi, A.; Mizushige, T.; Kitabayashi, N.; Tsuzuki, S.; Inoue, K.; Fushiki, T. Colocalization of GPR120 with phospholipase-Cbeta2 and alpha-gustducin in the taste bud cells in mice. Neurosci. Lett., 2009, 450, 186-90.
55. Martin, C.; Passilly-Degrace, P.; Gaillard, D.; Merlin, J.F.; Chevrot, M.; Besnard, P. The lipid-sensor candidates CD36 and GPR120 are differentially regulated by dietary lipids in mouse taste buds: impact on spontaneous fat preference. PLoS One. 2011, 6, e24014.
56. McGahon, B.M.; Martin, D.S.; Horrobin, D.F.; Lynch, M.A. Agerelated changes in synaptic function: analysis of the effect of dietary supplementation with omega-3 fatty acids. Neuroscience, 1999, 94, 305-314.
57. Kotani, S.; Sakaguchi, E.; Warashina, S.; Matsukawa, N.; Ishikura, Y.; Kiso, Y.; Sakakibara, M.; Yoshimoto, T.; Guo, J.; Yamashima, T. Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci. Res., 2006, 56, 159-164.
58. Ma, D.; Tao, B.; Warashina, S.; Kotani, S.; Lu, L.; Kaplamadzhiev, D.B.; Mori, Y.; Tonchev, A.B.; Yamashima, T. Expression of free fatty acid receptor GPR40 in the central nervous system of adult monkeys. Neurosci. Res., 2007, 58, 394-401.
59. Ma, D.; Lu, L.; Boneva, N.B.; Warashina, S.; Kaplamadzhiev, D.B.; Mori, Y.; Nakaya, M.A.; Kikuchi, M., Tonchev, A.B.; Okano, H.; Yamashima, T. Expression of free fatty acid receptor GPR40 in the neurogenic niche of adult monkey hippocampus. Hippocampus, 2008, 18, 326-333.
60. Boneva, N.B.; Yamashima, T. New insights into "GPR40-CREB interaction in adult neurogenesis" specific for primates. Hippocampus 2012, 22, 896-905.
61. Ma, D.; Zhang, M.; Larsen, C.P.; Xu, F.; Hua, W.; Yamashima, T.; Mao, Y.; Zhou, L. DHA promotes the neuronal differentiation of rat neural stem cells transfected withGPR40 gene. Brain Res., 2010, 1330, 1-8.
62. Nakamoto, K.; Nishinaka, T.; Matsumoto, K.; Kasuya, F.; Mankura, M.; Koyama, Y.; Tokuyama, S. Involvement of the longchain fatty acid receptor GPR40 as a novel pain regulatory system. Brain Res., 2012, 1432, 74-83.
63. Cornish, J.; MacGibbon, A.; Lin, J.M.; Watson, M.; Callon, K.E.; Tong, P.C.; Dunford, J.E.; van der Does, Y.; Williams, G.A.; Grey, A.B.; Naot, D.; Reid, I.R. Modulation of osteoclastogenesis by fatty acids. Endocrinology, 2008, 149, 5688-5695.
64. Gotoh, C.; Hong, Y.H.; Iga, T.; Hishikawa, D.; Suzuki, Y.; Song, S.H.; Choi, K.C.; Adachi, T.; Hirasawa, A.; Tsujimoto, G.; Sasaki, S.; Roh, S.G. The regulation of adipogenesis through GPR120. Biochem. Biophys. Res. Commun., 2007, 354, 591-597.
65. Steneberg, P., Rubins, N., Bartoov-Shifman, R., Walker, M.D., Edlund, H. The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse. Cell Metab., 2005, 1, 245-258.
66. Latour, M.G.; Alquier, T.; Oseid, E.; Tremblay, C.; Jetton, T.L.; Luo, J.; Lin, D.C.; Poitout, V. GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo. Diabetes, 2007, 56, 1087-1094.
67. Alquier, T.; Peyot, M.L.; Latour, M.G.; Kebede, M.; Sorensen, C.M.; Gesta, S.; Ronald Kahn, C.; Smith, R.D.; Jetton, T.L.; Metz, T.O.; Prentki, M.; Poitout, V. Deletion of GPR40 impairs glucoseinduced insulin secretion in vivo in mice without affecting intracellular fuel metabolism in islets. Diabetes, 2009, 58, 2607-2615.
68. Nagasumi, K.; Esaki, R.; Iwachidow, K.; Yasuhara, Y.; Ogi, K.; Tanaka, H.; Nakata, M.; Yano, T.; Shimakawa, K.; Taketomi, S.; Takeuchi, K.; Odaka, H.; Kaisho, Y. Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice. Diabetes, 2009, 58, 1067-1076.
69. Liou, A.P.; Lu, X.; Sei, Y.; Zhao, X.; Pechhold, S.; Carrero, R.J.; Raybould, H.E.; Wank, S. The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin. Gastroenterology, 2011, 140, 903-912.
70. Oh, D.Y.; Talukdar, S.; Bae, E.J.; Imamura, T.; Morinaga, H.; Fan, W.; Li, P.; Lu, W.J.; Watkins, S.M.; Olefsky, J.M. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell, 2010,142, 687-98.
71. Ichimura, A.; Hirasawa, A.; Poulain-Godefroy, O.; Bonnefond, A.; Hara, T.; Yengo, L.; Kimura, I.; Leloire, A.; Liu, N.; Iida, K.; Choquet, H.; Besnard, P.; Lecoeur, C.; Vivequin, S.; Ayukawa, K.; Takeuchi, M.; Ozawa, K.; Tauber, M.; Maffeis, C.; Morandi, A.; Buzzetti, R.; Elliott, P.; Pouta, A.; Jarvelin, M.R.; Körner, A.; Kiess, W.; Pigeyre, M.; Caiazzo, R.; Van Hul, W.; Van Gaal, L.; Horber, F.; Balkau, B.; Lévy-Marchal, C.; Rouskas, K.; Kouvatsi, A.; Hebebrand, J.; Hinney, A.; Scherag, A.; Pattou, F.; Meyre, D.; Koshimizu, T.A.; Wolowczuk, I.; Tsujimoto, G.; Froguel, P. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature, 2012, 483, 350-354.
72. Cao, H.; Gerhold, K.; Mayers, J.R.; Wiest, M.M.; Watkins, S.M.; Hotamisligil, G.S. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell, 2008, 134, 933-944.
73. Wittenberger, T.; Schaller, H.C.; Hellebrand, S. An expressed sequence tag (EST) data mining strategy succeeding in the discovery of new G-protein coupled receptors. J. Mol. Biol., 2001, 307, 799-813.
74. Yousefi, S.; Cooper, P.R.; Potter, S.L.; Mueck, B.; Jarai, G. Cloning and expression analysis of a novel G-protein-coupled receptor selectively expressed on granulocytes. J. Leukoc. Biol., 2001, 69, 1045-1052.
75. Lattin, J.E.; Schroder, K.; Su, A.I.; Walker, J.R.; Zhang, J.; Wiltshire, T.; Saijo, K., Glass, C.K.; Hume, D.A.; Kellie, S.; Sweet, M.J. Expression analysis of G Protein-Coupled Receptors in mouse macrophages. Immunome Res., 2008, 4, 5.
76. Hsieh, C.S.; Macatonia, S.E.; Tripp, C.S.; Wolf, S.F.; O'Garra, A.; Murphy, KM. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science, 1993, 260, 547-269.
77. Venkataraman, C.; Kuo, F. The G-protein coupled receptor, GPR84 regulates IL-4 production by T lymphocytes in response to CD3 crosslinking. Immunol. Lett., 2005, 101, 144-153.
78. Bouchard, C.; Pagé, J.; Bédard, A.; Tremblay, P.; Vallières, L. G protein-coupled receptor 84, a microglia-associated protein expressed in neuroinflammatory conditions. Glia, 2007, 55, 790-800.
79. Krakowski, M.L.; Owens, T. The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis. Eur. J. Immunol., 1997, 27, 2840-2847.
80. Perry, K.J.; Johnson, V.R.; Malloch, E.L.; Fukui, L.; Wever, J.; Thomas, A.G.; Hamilton, P.W.; Henry, J.J. The G-protein-coupled receptor, GPR84, is important for eye development in Xenopus laevis. Dev. Dyn., 2010, 239, 3024-3037.
81. Nagasaki, H.; Kondo, T.; Fuchigami, M.; Hashimoto, H.; Sugimura, Y.; Ozaki, N.; Arima, H.; Ota, A.; Oiso, Y.; Hamada, Y. Inflammatory changes in adipose tissue enhance expression of GPR84, a medium-chain fatty acid receptor: TNF enhances GPR84 expression in adipocytes. FEBS Lett., 2012, 586, 368-372.
82. Xiong, Y.; Miyamoto, N.; Shibata, K.; Valasek, M.A.; Motoike, T., Kedzierski, R.M., 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, 1045-1050.
83. Hong, Y.H.; Nishimura, Y.; Hishikawa, D.; Tsuzuki, H.; Miyahara, H.; Gotoh, C.; Choi, K.C.; Feng, D.D.; Chen, C.; Lee, H.G.; Katoh, K.; Roh, S.G.; Sasaki, S. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology, 2005, 146, 5092-5099.
84. Ge, H.; Li, X.; Weiszmann, J.; Wang, P.; Baribault, H.; Chen, J.L.; Tian, H.; Li, Y. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology, 2008, 149, 4519-4526.
85. Zaibi, M.S.; Stocker, C.J.; O'Dowd, J.; Davies, A.; Bellahcene, M.; Cawthorne, M.A.; Brown, A.J.; Smith, D.M.; Arch, J.R. Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids. FEBS Lett., 2010, 584, 2381-2386.
86. Senga, T.; Iwamoto, S.; Yoshida, T.; Yokota, T.; Adachi, K.; Azuma, E.; Hamaguchi, M.; Iwamoto, T. LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3. Blood, 2003, 101, 1185-1187.
87. Vinolo, M.A.; Ferguson, G.J.; Kulkarni, S.; Damoulakis, G.; Anderson, K.; Bohlooly-Y, M.; Stephens, L.; Hawkins, P.T.; Curi, R. SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor. PLoS One, 2011, 6, e21205.
88. Yonezawa, T.; Kobayashi, Y.; Obara, Y. Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast cancer cell line. Cell. Signal., 2007, 19, 185-193.
89. Yonezawa, T.; Haga, S.; Kobayashi, Y.; Katoh, K.; Obara, Y. Short-chain fatty acid signaling pathways in bovine mammary epithelial cells. Regul. Pept., 2009, 153, 30-36.
90. Hatanaka, H.; Tsukui, M.; Takada, S.; Kurashina, K.; Choi, Y.L.; Soda, M.; Yamashita, Y.; Haruta, H.; Hamada, T.; Ueno, T.; Tamada, K.; Hosoya, Y.; Sata, N.; Yasuda, Y.; Nagai, H.; Sugano, K.; Mano, H. Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening. Cancer Sci. 2010, 101, 54-59.
91. Tang, Y.; Chen, Y.; Jiang, H.; Robbins, G.T.; Nie, D. G-proteincoupled receptor for short-chain fatty acids suppresses colon cancer. Int. J. Cancer., 2011, 128, 847-856.
92. Karaki, S.; Mitsui, R.; Hayashi, H.; Kato, I.; Sugiya, H.; Iwanaga, T.; Furness, J.B.; Kuwahara, A. Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res., 2006, 324, 353-60.
93. Karaki, S.; Tazoe, H.; Hayashi, H.; Kashiwabara, H.; Tooyama, K.; Suzuki, Y.; Kuwahara, A. Expression of the short-chain fatty acid receptor, GPR43, in the human colon. J. Mol. Histol., 2008, 39, 135-142.
94. 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, 149-156.
95. Karaki, S.; Kuwahara, A. Propionate-induced epithelial K(+) and Cl(-)/HCO3(-) secretion and free fatty acid receptor 2 (FFA2, GPR43) expression in the guinea pig distal colon. Pflugers Arch., 2011, 461, 141-152.
96. Kaji, I.; Karaki, S.; Tanaka, R.; Kuwahara, A. Density distribution of free fatty acid receptor 2 (FFA2)-expressing and GLP-1-producing enteroendocrine L cells in human and rat lower intestine, and increased cell numbers after ingestion of fructooligosaccharide. J. Mol. Histol., 2011, 42, 27-38.
97. Yajima, T.; Inoue, R.; Yajima, M.; Tsuruta, T.; Karaki, S.; Hira, T.; Kuwahara, A. The G-protein on cholesterol-rich membrane microdomains mediates mucosal sensing of short-chain fatty acid and secretory response in rat colon. Acta Physiol. (Oxf)., 2011, 203, 381-389.
98. Tolhurst, G.; Heffron, H.; Lam, Y.S.; Parker, H.E.; Habib, A.M.; Diakogiannaki, E.; Cameron, J.; Grosse, J.; Reimann, F.; Gribble, F.M. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes, 2012, 61, 364-371.
99. Gregory, P.C. Control of intrinsic reticulo-ruminal motility in the vagotomized sheep. J. Physiol., 1984, 346, 379-393.
100. Dass, N.B.; John, A.K.; Bassil, A.K.; Crumbley, C.W.; Shehee, W.R.; Maurio, F.P.; Moore, G.B.; Taylor, C.M.; Sanger, G.J. The relationship between the effects of short-chain fatty acids on intestinal motility in vitro and GPR43 receptor activation. Neurogastroenterol. Motil., 2007, 19, 66-74.
101. Maslowski, K.M.; Vieira, A.T.; Ng, A.; Kranich, J.; Sierro, F.; Yu, D.; Schilter, H.C.; Rolph, M.S.; Mackay, F.; Artis, D.; Xavier, R.J.; Teixeira, M.M.; Mackay, C.R. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature, 2009, 461, 1282-1286.
102. Sina, C.; Gavrilova, O.; Förster, M.; Till, A.; Derer, S.; Hildebrand, F.; Raabe, B.; Chalaris, A.; Scheller, J.; Rehmann, A.; Franke, A.; Ott, S.; Häsler, R.; Nikolaus, S.; Fölsch, U.R.; Rose-John, S.; Jiang, H.P.; Li, J.; Schreiber, S.; Rosenstiel, P. G. protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J. Immunol., 2009, 183, 7514-7522.
103. Bäckhed, F.; Ding, H.; Wang, T.; Hooper, L.V.; Koh, G.Y.; Nagy, A.; Semenkovich, C.F.; Gordon, J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. U. S. A., 2004, 101, 15718-15723.
104. Samuel, B.S.; Shaito, A.; Motoike, T.; Rey, F.E.; Backhed, F.; Manchester, J.K.; Hammer, R.E.; Williams, S.C.; Crowley, J.; Yanagisawa, M.; Gordon, J.I. 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., U S A., 2008, 105, 16767-16772.
105. 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. U. S. A., 2011, 108, 8030-8035.
106. Bjursell, M.; Admyre, T.; Göransson, M.; Marley, A.E.; Smith, D.M.; Oscarsson, J.; Bohlooly-Y, M. Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet. Am. J. Physiol. Endocrinol. Metab., 2011, 300, E211-220.
107. Garrido, D.M.; Corbett, D.F.; Dwornik, K.A.; Goetz, A.S.; Littleton, T.R.; McKeown, S.C.; Mills, W.Y.; Smalley, T.L. Jr; Briscoe, C.P.; Peat, A.J. Synthesis and activity of small molecule GPR40 agonists. Bioorg. Med. Chem. Lett., 2006, 16, 1840-1845.
108. Briscoe, C.P.; Peat, A.J.; McKeown, S.C.; Corbett, D.F.; Goetz, A.S.; Littleton, T.R.; McCoy, D.C.; Kenakin, T.P.; Andrews, J.L.; Ammala, C.; Fornwald, J.A.; Ignar, D.M.; Jenkinson, S. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br. J. Pharmacol., 2006, 148, 619-628.
109. McKeown, S.C.; Corbett, D.F.; Goetz, A.S.; Littleton, T.R.; Bigham, E.; Briscoe, C.P.; Peat, A.J.; Watson, S.P.; Hickey, D.M. Solid phase synthesis and SAR of small molecule agonists for the GPR40 receptor. Bioorg. Med. Chem. Lett., 2007, 17, 1584-1589.
110. Tikhonova, I.G.; Sum, C.S.; Neumann, S.; Thomas, C.J.; Raaka, B.M.; Costanzi, S.; Gershengorn, M.C. Bidirectional, iterative approach to the structural delineation of the functional "chemoprint" in GPR40 for agonist recognition. J. Med. Chem., 2007, 50, 2981-2989.
111. Sum, C.S.; Tikhonova, I.G.; Neumann, S.; Engel, S.; Raaka, B.M.; Costanzi, S.; Gershengorn, M.C. Identification of residues important for agonist recognition and activation in GPR40. J. Biol. Chem., 2007, 282, 29248-29255.
112. Song, F.; Lu, S.; Gunnet, J.; Xu, J.Z.; Wines, P.; Proost, J.; Liang, Y.; Baumann, C.; Lenhard, J.; Murray, W.V.; Demarest, K.T.; Kuo, G.H. Synthesis and biological evaluation of 3-aryl-3-(4-phenoxy)-propionic acid as a novel series of G protein-coupled receptor 40 agonists. J. Med. Chem., 2007, 50, 2807-2817.
113. Bharate, S.B.; Rodge, A.; Joshi, R.K.; Kaur, J.; Srinivasan, S.; Kumar, S.S.; Kulkarni-Almeida, A.; Balachandran, S.; Balakrishnan, A.; Vishwakarma, R.A. Discovery of diacylphloroglucinols as a new class of GPR40 (FFAR1) agonists. Bioorg. Med. Chem. Lett., 2008, 18, 6357-6361.
114. Christiansen, E.; Urban, C.; Merten, N.; Liebscher, K.; Karlsen, K.K.; Hamacher, A.; Spinrath, A.; Bond, A.D.; Drewke, C.; Ullrich, S.; Kassack, M.U.; Kostenis, E.; Ulven, T. Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)/GPR40), a potential target for the treatment of type II diabetes. J. Med. Chem., 2008, 51, 7061-7064.
115. Tikhonova, I.G.; Sum, C.S.; Neumann, S.; Engel, S.; Raaka, B.M.; Costanzi, S.; Gershengorn, M.C. Discovery of novel agonists and antagonists of the free fatty acid receptor 1 (FFAR1) usingvirtual screening. J. Med. Chem., 2008, 51, 625-633.
116. Humphries, P.S.; Benbow, J.W.; Bonin, P.D.; Boyer, D.; Doran, S.D.; Frisbie, R.K.; Piotrowski, D.W.; Balan, G.; Bechle, B.M.; Conn, E.L.; Dirico, K.J.; Oliver, R.M.; Soeller, W.C.; Southers, J.A.; Yang, X. Synthesis and SAR of 1,2,3,4-tetrahydroisoquinolin-1-ones as novel G-protein-coupled receptor 40 (GPR40) antagonists. Bioorg. Med. Chem. Lett., 2009,19, 2400-2403.
117. Negoro, N.; Sasaki, S.; Mikami, S.; Ito, M.; Suzuki, M.; Tsujihata, Y.; Ito, R.; Harada, A.; Takeuchi, K.; Suzuki, N.; Miyazaki, J.; Santou, T.; Odani, T.; Kanzaki, N.; Funami, M.; Tanaka, T.; Kogame, A.; Matsunaga, S.; Yasuma, T.; Momose, Y. Discovery of TAK-875: a potent, selective, and orally bioavailable GPR40 agonist. ACS Med. Chem. Lett,. 2010, 1, 290-294.
118. Naik, H.; Vakilynejad, M.; Wu, J.; Viswanathan, P.; Dote, N.; Higuchi, T.; Leifke, E. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Properties of the GPR40Agonist TAK-875: Results From a Double-Blind, Placebo-Controlled Single Oral Dose RisingStudy in Healthy Volunteers. J Clin Pharmacol. 2011, 52, 1007-1016.
119. Burant, C.F.; Viswanathan, P.; Marcinak, J.; Cao, C.; Vakilynejad, M.; Xie, B.; Leifke, E. TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet, 2012, 379, 1403-1411.
120. Takeuchi, M.; Hirasawa, A.; Hara, T.; Kimura, I.; Hirano, T.; Suzuki, T.; Miyata, N.; Awaji, T.; Ishiguro, M.; Tsujimoto, G. FFA1-selective agonistic activity based on docking simulation using FFA1 and GPR120 homology models. Br. J. Pharmacol. 2012 May 28. doi: 10.1111/j.1476-5381.2012.02052.x. [Epub ahead of print]
121. Suzuki, T.; Igari, S.; Hirasawa, A.; Hata, M.; Ishiguro, M.; Fujieda, H.; Itoh, Y.; Hirano, T.; Nakagawa, H.; Ogura, M.; Makishima, M.; Tsujimoto, G.; Miyata, N. Identification of G proteincoupled receptor 120-selective agonists derived fromPPARgamma agonists. J. Med. Chem., 2008, 51, 7640-7644.
122. Hara, T.; Hirasawa, A.; Sun, Q.; Sadakane, K.; Itsubo, C.; Iga, T.; Adachi, T.; Koshimizu, T.A.; Hashimoto, T.; Asakawa, Y.; Tsujimoto, G. Novel selective ligands for free fatty acid receptors GPR120 and GPR40. Naunyn. Schmiedebergs Arch. Pharmacol., 2009, 380, 247-255.
123. Shimpukade, B.; Hudson, B.D.; Hovgaard, C.K.; Milligan, G.; Ulven, T. Discovery of a potent and selective GPR120 agonist. J. Med. Chem. 2012, 55, 4511-4515.
124. Lee, T.; Schwandner, R.; Swaminath, G., Weiszmann, J.; Cardozo, M.; Greenberg, J.; Jaeckel, P.; Ge, H.; Wang, Y.; Jiao, X.; Liu, J.; Kayser, F.; Tian, H.; Li, Y. Identification and functional characterization of allosteric agonists for the G protein-coupled receptor FFA2. Mol. Pharmacol., 2008, 74, 1599-1609.
125. Wang, Y.; Jiao, X.; Kayser, F.; Liu, J.; Wang, Z.; Wanska, M.; Greenberg, J.; Weiszmann, J.; Ge, H.; Tian, H.; Wong, S.; Schwandner, R.; Lee, T.; Li, Y. The first synthetic agonists of FFA2: Discovery and SAR of phenylacetamides as allosteric modulators. Bioorg. Med. Chem. Lett., 2010, 20, 493-498.
126. Smith, N.J.; Ward, R.J.; Stoddart, L.A.; Hudson, B.D.; Kostenis, E.; Ulven, T.; Morris, J.C.; Tränkle, C.; Tikhonova, I.G.; Adams, D.R.; Milligan, G. Extracellular loop 2 of the free fatty acid receptor 2 mediates allosterism of a phenylacetamide agoallosteric modulator. Mol. Pharmacol., 2011, 80, 163-173.
127. Tiwari, A. GPR43: an emerging target for the potential treatment of type 2 diabetes, obesity and insulin resistance. Curr. Opin. Investig. Drugs., 2010, 11, 385-393.
128. Schmidt, J.; Smith, N.J.; Christiansen, E.; Tikhonova, I.G.; Grundmann, M.; Hudson, B.D.; Ward, R.J.; Drewke, C.; Milligan, G.; Kostenis, E.; Ulven, T. Selective orthosteric free fatty acid receptor 2 (FFA2) agonists: identification of the structural and chemical requirements for selective activation of FFA2 versus FFA3. J. Biol. Chem., 2011, 286, 10628-10640.
129. Takeda, S.; Yamamoto, A.; Okada, T.; Matsumura, E.; Nose, E.; Kogure, K.; Kojima, S.; Haga, T. Identification of surrogate ligands for orphan G protein-coupled receptors. Life Sci., 2003, 74, 367-377.