Abstract

G protein-coupled receptors (GPCRs) constitute a family of transmembrane proteins that mediate many cellular processes. GPR120/FFAR4, a receptor from this family that is activated by fatty acids, has received considerable attention recently. This paper presents a literature review concerning the role of GPR120 and its mechanism of action in animal and human studies as well as the potential use of GPR120 for the treatment of chronic diseases. Two electronic databases – Medline and Google Scholar – were searched for available studies addressing the review topic that were written in English and published from 2000 to June 2017. The following key terms were used in the search: GPR120, FFA4, GPR120 agonist, PUFAs, EPA, DHA, adipocyte, obesity, hyperlipidemia, inflammation, cancer, diabetes, insulin resistance, taste, atherogenesis, hepatis, central nervous system. In humans, GPR120 expression is expressed in macrophages, eosinophils, and adipose tissue, in cells of the tongue, liver, lungs, small and large intestine, gastric mucosa, and pancreas, in the central nervous system and placental microvilli. Medium- and long-chain fatty acids act as ligands for the receptor. Through the internalization of beta-arrestin-2 complex and the inhibition of NF-κB, GPR120 mediates the activation of the cell’s anti-inflammatory mechanisms. The receptor is also involved in the maturation of adipocytes, the modulation of insulin signalling pathways, the regulation of glucose metabolism, and the secretion of intestinal hormones. GPR120 is a promising target for the treatment of numerous diseases, whose pathophysiology is associated with low-grade inflammation. As a result of intensive searches, a likely group of synthetic agonists of the receptor was determined with potential therapeutic applications in conditions such as obesity, impaired carbohydrate metabolism, inflammatory bowel diseases, cancer, mental disorders.

References

• 1. Adachi N., Numakawa T., Richards M., Nakajima S., Kunugi H.: New insight in expression, transport, and secretion of brain-derived neurotrophic factor: implications in brain-related diseases. World J. Biol. Chem., 2014; 5: 409-428
  Google Scholar
• 2. Adams G.L., Velazquez F., Jayne C., Shah U., Miao S., Ashley E.R., Madeira M., Akiyama T.E., Di Salvo J., Suzuki T., Wang N., Truong Q., Gilbert E., Zhou D., Verras A. i wsp.: Discovery of chromane propionic acid analogues as selective agonists of GPR120 with in vivo activity in rodents. ACS Med. Chem. Lett., 2016; 8: 96-101
  Google Scholar
• 3. Ahn S.H., Park S.Y., Baek J.E., Lee S.Y., Baek W.Y., Lee S.Y., Lee Y.S., Yoo H.J., Kim H., Lee S.H., Im D.S., Lee S.K., Kim B.J., Koh J.M.: Free fatty acid receptor 4 (GPR120) stimulates bone formation and suppresses bone resorption in the presence of elevated n-3 fatty acid levels. Endocrinology, 2016; 157: 2621-2635
  Google Scholar
• 4. Alkahtani R., Mahavadi S., Alqudah M., Murthy K., Grider J.: Activation of long-chain free fatty acid receptor FFAR1 (GPR40) and FFAR4 (GPR120) causes release of brain-derived neurotropic factor from enteric glial cells (905.2). FASEB J., 2014; 28 (Suppl. 1): 905.2
  Google Scholar
• 5. Anbazhagan A.N., Priyamvada S., Gujral T., Bhattacharyya S., Alrefai W.A., Dudeja P.K., Borthakur A.: A novel anti-inflammatory role of GPR120 in intestinal epithelial cells. Am. J. Physiol. Cell Physiol., 2016; 310: C612-C621
  Google Scholar
• 6. Ancel D., Bernard A., Subramaniam S., Hirasawa A., Tsujimoto G., Hashimoto T., Passilly-Degrace P., Khan N.A., Besnard P.: The oral lipid sensor GPR120 is not indispensable for the orosensory detection of dietary lipids in mice. J. Lipid Res., 2015; 56: 369-378
  Google Scholar
• 7. Auguste S., Fisette A., Fernandes M.F., Hryhorczuk C., Poitout V., Alquier T., Fulton S.: Central agonism of GPR120 acutely inhibits food intake and food reward and chronically suppresses anxiety-like behavior in mice. Int. J. Neuropsychopharmacol., 2016; 19: pyw014
  Google Scholar
• 8. Besnard P., Passilly-Degrace P., Khan N.A.: Taste of fat: a sixth taste modality? Physiol. Rev., 2016; 96: 151-176
  Google Scholar
• 9. Bjursell M., Xu X., Admyre T., Böttcher G., Lundin S., Nilsson R., Stone V.M., Morgan N.G., Lam Y.Y., Storlien L.H., Lindén D., Smith D.M., Bohlooly-Y M., Oscarsson J.: The beneficial effects of n-3 polyunsaturated fatty acids on diet induced obesity and impaired glucose control do not require Gpr120. PLoS One, 2014; 9: e114942
  Google Scholar
• 10. Bonnefond A., Lamri A., Leloire A., Vaillant E., Roussel R., Lévy-Marchal C., Weill J., Galan P., Hercberg S., Ragot S., Hadjadj S., Charpentier G., Balkau B., Marre M., Fumeron F., Froguel P.: Contribution of the low- -frequency, loss-of-function p.R270H mutation in FFAR4 (GPR120) to increased fasting plasma glucose levels. J. Med. Genet., 2015; 52: 595-598
  Google Scholar
• 11. 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. i wsp.: 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
  Google Scholar
• 12. Burns R.N., Moniri N.H.: Agonism with the omega-3 fatty acids α-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor. Biochem. Biophys. Res. Commun., 2010; 396: 1030-1035
  Google Scholar
• 13. 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; 30: 8376-8382
  Google Scholar
• 14. Chelliah M., Chu H.D., Cox J.M., Debenham J.S., Eagen K., Lan P., London C., Plotkin M.A., Shah U., Sinz C.J., Sun Z., Vaccaro H.M., Venkatraman S.: Substituted spiropiperidinyl compounds useful as gpr120 agonists. Patent US 20150274672 (2015). https://www.google.com/patents/US20150274672 (26.03.2017)
  Google Scholar
• 15. Cheshmehkani A., Senatorov I.S., Kandi P., Singh M., Britt A., Hayslett R., Moniri N.H.: Fish oil and flax seed oil supplemented diets increase FFAR4 expression in the rat colon. Inflamm. Res., 2015; 64: 809-815
  Google Scholar
• 16. Cornall L.M., Mathai M.L., Hryciw D.H., McAinch A.J.: Diet-induced obesity up-regulates the abundance of GPR43 and GPR120 in a tissue specific manner. Cell. Physiol. Biochem., 2011; 28: 949-958
  Google Scholar
• 17. Cox J.M., Chu H.D., Chelliah M.V., Debenham J.S., Eagen K., Lan P., Lombardo M., London C., Plotkin M.A., Shah U., Sun Z., Vaccaro H.M., Venkatraman S., Suzuki T., Wang N. i wsp.: Design, synthesis, and evaluation of novel and selective G-protein coupled receptor 120 (GPR120) spirocyclic agonists. ACS Med. Chem. Lett., 2016; 8: 49-54
  Google Scholar
• 18. Engelstoft M.S., Park W.M., Sakata I., Kristensen L.V., Husted A.S., Osborne-Lawrence S., Piper P.K., Walker A.K., Pedersen M.H., Nøhr M.K., Pan J., Sinz C.J., Carrington P.E., Akiyama T.E., Jones R.M. i wsp.: Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Mol. Metab., 2013; 2: 376-392
  Google Scholar
• 19. FFAR4 free fatty acid receptor 4 [Homo sapiens (human)] https:// www.ncbi.nlm.nih.gov/gene/338557 (03.04.2017)
  Google Scholar
• 20. Formicola R., Pevarello P., Kuhn C., Liberati C., Piscitelli F., Sodano M.: FFA4/GPR120 agonists: a survey of the recent patent literature. Pharm. Pat. Anal., 2015; 4: 443-451
  Google Scholar
• 21. Fredborg M., Theil P.K., Jensen B.B., Purup S.: G protein-coupled receptor120 (GPR120) transcription in intestinal epithelial cells is significantly affected by bacteria belonging to the Bacteroides, Proteobacteria, and Firmicutes phyla. J. Anim. Sci., 2012; 90 (Suppl. 4): 10-12
  Google Scholar
• 22. Fredriksson R., Lagerström M.C., Lundin L.G., Schiöth H.B.: The G- -protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol., 2003; 63: 1256-1272
  Google Scholar
• 23. Fukushima K., Yamasaki E., Ishii S., Tomimatsu A., Takahashi K., Hirane M., Fukushima N., Honoki K., Tsujiuchi T.: Different roles of GPR120 and GPR40 in the acquisition of malignant properties in pancreatic cancer cells. Biochem. Biophys. Res. Commun., 2015; 465: 512-515
  Google Scholar
• 24. Furutani A., Ikeda Y., Itokawa M., Nagahama H., Ohtsu T., Furutani N., Kamagata M., Yang Z.H., Hirasawa A., Tahara Y., Shibata S.: Fish oil accelerates diet-induced entrainment of the mouse peripheral clock via GPR120. PLoS One, 2015; 10: e0132472
  Google Scholar
• 25. 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
  Google Scholar
• 26. Godinot N., Yasumatsu K., Barcos M.E., Pineau N., Ledda M., Viton F., Ninomiya Y., le Coutre J., Damak S.: Activation of tongue-expressed GPR40 and GPR120 by non caloric agonists is not sufficient to drive preference in mice. Neuroscience, 2013; 250: 20-30
  Google Scholar
• 27. Gong Z., Yoshimura M., Aizawa S., Kurotani R., Zigman J.M., Sakai T., Sakata I.: G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro. Am. J. Physiol. Endocrinol. Metab., 2014; 306: 28-35
  Google Scholar
• 28. 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
  Google Scholar
• 29. Gozal D., Kheirandish-Gozal L., Carreras A., Khalyfa A., Peris E.: Obstructive sleep apnea and obesity are associated with reduced GPR 120 plasma levels in children. Sleep, 2014; 37: 935-941
  Google Scholar
• 30. 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
  Google Scholar
• 31. 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. i wsp.: Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature, 2012; 483: 350-354
  Google Scholar
• 32. Im D.S.: Intercellular lipid mediators and GPCR drug discovery. Biomol. Ther., 2013; 21: 411-422
  Google Scholar
• 33. Iwasaki K., Harada N., Sasaki K., Yamane S., Iida K., Suzuki K., Hamasaki A., Nasteska D., Shibue K., Joo E., Harada T., Hashimoto T., Asakawa Y., Hirasawa A., Inagaki N.: Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion. Endocrinology, 2015; 156: 837-846
  Google Scholar
• 34. 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
  Google Scholar
• 35. Kim H.J., Yoon H.J., Kim B.K., Kang W.Y., Seong S.J., Lim M.S., Kim S.Y., Yoon Y.R.: G protein-coupled receptor 120 signaling negatively regulates osteoclast differentiation, survival, and function. J. Cell. Physiol., 2016; 231: 844-851
  Google Scholar
• 36. Kim N., Lee J.O., Lee H.J., Kim H.I., Kim J.K., Lee Y.W., Lee S.K., Kim S.J., Park S.H., Kim H.S.: Endogenous ligand for GPR120, docosahexaenoic acid, exerts benign metabolic effects on the skeletal muscles via AMP- -activated protein kinase pathway. J. Biol. Chem., 2015; 290: 20438-20447
  Google Scholar
• 37. Kita T., Kadochi Y., Takahashi K., Fukushima K., Yamasaki E., Uemoto T., Hirane M., Fukushima N., Honoki K., Tsujiuchi T.: Diverse effects of G-protein-coupled free fatty acid receptors on the regulation of cellular functions in lung cancer cells. Exp. Cell Res., 2016; 342: 193-199
  Google Scholar
• 38. Konno Y., Ueki S., Takeda M., Kobayashi Y., Tamaki M., Moritoki Y., Oyamada H., Itoga M., Kayaba H., Omokawa A., Hirokawa M.: Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis. PLoS One, 2015; 10: e0120386
  Google Scholar
• 39. Lager S., Ramirez V.I., Gaccioli F., Jansson T., Powell T.L.: Expression and localization of the omega-3 fatty acid receptor GPR120 in human term placenta. Placenta, 2014; 35: 523-525
  Google Scholar
• 40. Lamri A., Bonnefond A., Meyre D., Balkau B., Roussel R., Marre M., Froguel P., Fumeron F.: Interaction between GPR120 p.R270H loss-of- -function variant and dietary fat intake on incident type 2 diabetes risk in the D.E.S.I.R. study. Nutr. Metab. Cardiovasc. Dis., 2016; 26: 931-936
  Google Scholar
• 41. Li X., Yu Y., Funk C.D.: Cyclooxygenase-2 induction in macrophages is modulated by docosahexaenoic acid via interactions with free fatty acid receptor 4 (FFA4). FASEB J., 2013; 27: 4987-4997
  Google Scholar
• 42. Little T.J., Isaacs N.J., Young R.L., Ott R., Nguyen N.Q., Rayner C.K., Horowitz M., Feinle-Bisset C.: Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index. Am. J. Physiol. Gastrointest. Liver Physiol., 2014; 307: G958-G967
  Google Scholar
• 43. Liu Y., Chen L.Y., Sokolowska M., Eberlein M., Alsaaty S., Martinez- -Anton A., Logun C., Qi H.Y., Shelhamer J.H.: The fish oil ingredient, docosahexaenoic acid, activates cytosolic phospholipase A₂ via GPR120 receptor to produce prostaglandin E₂ and plays an anti-inflammatory role in macrophages. Immunology, 2014; 143: 81-95
  Google Scholar
• 44. Liu Z., Hopkins M.M., Zhang Z., Quisenberry C.B., Fix L.C., Galvan B.M., Meier K.E.: Omega-3 fatty acids and other FFA4 agonists inhibit growth factor signaling in human prostate cancer cells. J. Pharmacol. Exp. Ther., 2015; 352: 380-394
  Google Scholar
• 45. Lombardo M., Bender K., London C., Plotkin M.A., Kirkland M., Mane J., Pachanski M., Geissler W., Cummings J., Habulihaz B., Akiyama T.E., Di Salvo J., Madeira M., Pols J., Powles M.A. i wsp.: Discovery of benzofuran propanoic acid GPR120 agonists: From uHTS hit to mechanism-based pharmacodynamic effects. Bioorg. Med. Chem. Lett., 2016; 26: 5724-5728
  Google Scholar
• 46. Martin C., Passilly-Degrace P., Chevrot M., Ancel D., Sparks S.M., Drucker D.J., Besnard P.: Lipid-mediated release of GLP-1 by mouse taste buds from circumvallate papillae: putative involvement of GPR120 and impact on taste sensitivity. J. Lipid Res., 2012; 53: 2256-2265
  Google Scholar
• 47. 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
  Google Scholar
• 48. Marzuillo P., Grandone A., Conte M., Capuano F., Cirillo G., Di Sessa A., Umano G.R., Romano R., Perrone L., del Giudice E.M.: Novel association between a nonsynonymous variant (R270H) of the G-protein-coupled receptor 120 and liver injury in children and adolescents with obesity. J. Pediatr. Gastroenterol. Nutr., 2014; 59: 472-475
  Google Scholar
• 49. 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
  Google Scholar
• 50. Milligan G., Alvarez-Curto E., Watterson K.R., Ulven T., Hudson B.D.: Characterizing pharmacological ligands to study the long-chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4. Br. J. Pharmacol., 2015; 172: 3254-3265
  Google Scholar
• 51. Milligan G., Kostenis E.: Heterotrimeric G-proteins: a short history. Br. J. Pharmacol. 2006; 147 (Suppl. S1): S46-S55
  Google Scholar
• 52. Moore K., Zhang Q., Murgolo N., Hosted T., Duffy R.: Cloning, expression, and pharmacological characterization of the GPR120 free fatty acid receptor from cynomolgus monkey: comparison with human GPR120 splice variants. Comp. Biochem. Physiol. B. Biochem. Mol. Biol., 2009; 154: 419-426
  Google Scholar
• 53. Moriyama R., Deura C., Imoto S., Nose K., Fukushima N.: Expression of the long-chain fatty acid receptor GPR120 in the gonadotropes of the mouse anterior pituitary gland. Histochem. Cell Biol., 2015; 143: 21-27
  Google Scholar
• 54. 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. TNFα enhances GPR84 expression in adipocytes. FEBS Lett., 2012; 586: 368-372
  Google Scholar
• 55. Nobili V., Carpino G., Alisi A., De Vito R., Franchitto A., Alpini G., Onori P., Gaudio E.: Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease. PLoS One, 2014; 9: e88005
  Google Scholar
• 56. 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: 687-698
  Google Scholar
• 57. Oh D.Y., Walenta E., Akiyama T.E., Lagakos W.S., Lackey D., Pessentheiner A.R., Sasik R., Hah N., Chi T.J., Cox J.M., Powels M.A., Di Salvo J., Sinz C., Watkins S.M., Armando A.M. i wsp.: A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nat. Med., 2014; 20: 942-947
  Google Scholar
• 58. Ozdener M.H., Subramaniam S., Sundaresan S., Sery O., Hashimoto T., Asakawa Y., Besnard P., Abumrad N.A., Khan N.A.: CD36 – and GPR120- -mediated Ca²⁺ signaling in human taste bud cells mediates differential responses to fatty acids and is altered in obese mice. Gastroenterology, 2014; 146: 995-1005
  Google Scholar
• 59. Pærregaard S.I., Agerholm M., Serup A.K., Ma T., Kiens B., Madsen L., Kristiansen K., Jensen B.A.: FFAR4 (GPR120) signaling is not required for anti-inflammatory and insulin-sensitizing effects of omega-3 fatty acids. Mediators Inflamm., 2016; 2016: 1536047
  Google Scholar
• 60. Paulsen S.J., Larsen L.K., Hansen G., Chelur S., Larsen P.J., Vrang N.: Expression of the fatty acid receptor GPR120 in the gut of diet-induced- -obese rats and its role in GLP-1 secretion. PLoS One, 2014; 9: e88227
  Google Scholar
• 61. Pawełczyk T., Grancow-Grabka M., Kotlicka-Antczak M., Trafalska E., Pawełczyk A.: A randomized controlled study of the efficacy of six- -month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. J. Psychiatr. Res., 2016; 73: 34-44
  Google Scholar
• 62. Raptis D.A., Limani P., Jang J.H., Ungethüm U., Tschuor C., Graf R., Humar B., Clavien P.A.: GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids. J. Hepatol., 2014; 60: 625-632
  Google Scholar
• 63. Rodriguez-Pacheco F., Garcia-Serrano S., Garcia-Escobar E., Gutierrez-Repiso C., Garcia-Arnes J., Valdes S., Gonzalo M., Soriguer F., Moreno-Ruiz F.J., Rodriguez-Cañete A., Gallego-Perales J.L., Martinez-Ferriz A., Rojo-Martínez G., Garcia-Fuentes E.: Effects of obesity/fatty acids on the expression of GPR120. Mol. Nutr. Food. Res., 2014; 58: 1852-1860
  Google Scholar
• 64. Satapati S., Qian Y., Wu M.S., Petrov A., Dai G., Wang S.P., Zhu Y., Shen X., Muise E.S., Chen Y., Zycband E., Weinglass A., Di Salvo J., Debenham J.S., Cox J.M. i wsp.: GPR120 suppresses adipose tissue lipolysis and synergizes with GPR40 in antidiabetic efficacy. J. Lipid Res., 2017; 58: 1561-1578
  Google Scholar
• 65. Shewale S.V., Brown A.L., Bi X., Boudyguina E., Sawyer J.K., Alexander-Miller M.A., Parks J.S.: In vivo activation of leukocyte GPR120/ FFAR4 by PUFAs has minimal impact on atherosclerosis in LDL receptor knockout mice. J. Lipid Res., 2017; 58: 236-246
  Google Scholar
• 66. 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; 377: 523-527
  Google Scholar
• 67. Tran D.Q., Ramos E.H., Belsham D.D.: Induction of Gnrh mRNA expression by the ω-3 polyunsaturated fatty acid docosahexaenoic acid and the saturated fatty acid palmitate in a GnRH-synthesizing neuronal cell model, mHypoA-GnRH/GFP. Mol. Cell. Endocrinol., 2016; 426: 125-135
  Google Scholar
• 68. Vestmar M.A., Andersson E.A., Christensen C.R., Hauge M., Glümer C., Linneberg A., Witte D.R., Jørgensen M.E., Christensen C., Brandslund I., Lauritzen T., Pedersen O., Holst B., Grarup N., Schwartz T.W., Hansen T.: Functional and genetic epidemiological characterisation of the FFAR4 (GPR120) p.R270H variant in the Danish population. J. Med. Genet., 2016; 53: 616-623
  Google Scholar
• 69. Waguri T., Goda T., Kasezawa N., Yamakawa-Kobayashi K.: The combined effects of genetic variations in the GPR120 gene and dietary fat intake on obesity risk. Biomed. Res., 2013; 34: 69-74
  Google Scholar
• 70. Wellhauser L., Belsham D.D.: Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons. J. Neuroinflammation, 2014; 11: 60
  Google Scholar
• 71. Westhoff G., Grayson B., Barker D., Morris C., Thornburg K., O’Tierney P.: The expression of the omega-3 fatty acid receptor, GPR120, is more sensitive to inflammatory cytokines and maternal obesity in male infants than in females. Am. J. Obstet. Gynecol., 2012; 206 (Suppl. 1): S360
  Google Scholar
• 72. Widmayer P., Küper M., Kramer M., Königsrainer A., Breer H.: Altered expression of gustatory-signaling elements in gastric tissue of morbidly obese patients. Int. J. Obes., 2012; 36: 1353-1359
  Google Scholar
• 73. Wu Q., Wang H., Zhao X., Shi Y., Jin M., Wan B., Xu H., Cheng Y., Ge H., Zhang Y.: Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma. Oncogene, 2013; 32: 5541-5550
  Google Scholar
• 74. Xu T., Sun Y., Sun W., Yao L., Sun L., Liu L., Ma J., Wang L.: Effect of omega-3 fatty acid supplementation on serum lipids and vascular inflammation in patients with end-stage renal disease: a meta-analysis. Sci. Rep., 2016; 6: 39346
  Google Scholar
• 75. Yang S.Y., Kim Y.S., Lee J.E., Seol J., Song J.H., Chung G.E., Yim J.Y., Lim S.H., Kim J.S.: Dietary protein and fat intake in relation to risk of colorectal adenoma in Korean. Medicine, 2016; 95: e5453
  Google Scholar
• 76. Yao J.K., Dougherty G.G. Jr., Gautier C.H., Haas G.L., Condray R., Kasckow J.W., Kisslinger B.L., Gurklis J.A., Messamore E.: Prevalence and specificity of the abnormal niacin response: a potential endophenotype marker in schizophrenia. Schizophr. Bull., 2016; 42: 369-376
  Google Scholar
• 77. Yin J., Li H., Meng C., Chen D., Chen Z., Wang Y., Wang Z., Chen G.: Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein- -coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway. Int. J. Biochem. Cell Biol., 2016; 75: 11-22
  Google Scholar
• 78. Zhang D., Leung P.S.: Potential roles of GPR120 and its agonists in the management of diabetes. Drug Des. Devel. Ther., 2014; 8: 1013-1027
  Google Scholar
• 79. Zhang D., So W.Y., Wang Y., Wu S.Y., Cheng Q., Leung P.S.: Insulinotropic effects of GPR120 agonists are altered in obese diabetic and obese non-diabetic states. Clin. Sci., 2017; 131: 247-260
  Google Scholar
• 80. Zhao J., Wang H., Shi P., Wang W., Sun Y.: GPR120, a potential therapeutic target for experimental colitis in IL-10 deficient mice. Oncotarget, 2017; 8: 8397-8405
  Google Scholar
• 81. Zhao Y., Zha D., Wang L., Qiao L., Lu L., Mei L., Chen C., Qiu J.: Phenotypic characterization of GPR120-expressing cells in the interstitial tissue of pancreas. Tissue Cell, 2013; 45: 421-427
  Google Scholar

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