It is well known that the amount and type of ingested fat impacts the development of obesity and metabolic diseases, but the potential for beneficial effects from fat has received less attention. It is becoming clear that the composition of the individual fatty acids in diet is important. Besides acting as precursors of potent signaling molecules, dietary fatty acids act directly on intracellular and cell surface receptors. The free fatty acid receptor 4 (FFA4, previously GPR120) is linked to the regulation of body weight, inflammation, and insulin resistance and represents a potential target for the treatment of metabolic disorders, including type 2 diabetes and obesity. In this review, we discuss the various types of dietary fatty acids, the link between FFA4 and metabolic diseases, the potential effects of the individual fatty acids on health, and the ability of fatty acids to activate FFA4. We also discuss the possibility of dietary schemes that implement activation of FFA4.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Adachi T, Yanaka H, Kanai H, Nozaki M, Takahara Y. 1.  et al. 2008. Administration of perilla oil coated with Calshell increases glucagon-like peptide secretion. Biol. Pharm. Bull. 31:1021–23 [Google Scholar]
  2. Arterburn LM, Hall EB, Oken H. 2.  2006. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am. J. Clin. Nutr. 83:S1467–76 [Google Scholar]
  3. Astrup A. 3.  2014. A changing view on saturated fatty acids and dairy: from enemy to friend. Am. J. Clin. Nutr. 100:1407–8 [Google Scholar]
  4. Axelsen LN, Keung W, Pedersen HD, Meier E, Riber D. 4.  et al. 2012. Glucagon and a glucagon-GLP-1 dual-agonist increases cardiac performance with different metabolic effects in insulin-resistant hearts. Br. J. Pharmacol. 165:2736–48 [Google Scholar]
  5. Back M, Dahlen SE, Drazen JM, Evans JF, Serhan CN. 5.  et al. 2011. International Union of Basic and Clinical Pharmacology. LXXXIV: leukotriene receptor nomenclature, distribution, and pathophysiological functions. Pharmacol. Rev. 63:539–84 [Google Scholar]
  6. Banz WJ, Davis JE, Clough RW, Cheatwood JL. 6.  2012. Stearidonic acid: Is there a role in the prevention and management of type 2 diabetes mellitus?. J. Nutr. 142:635–40S [Google Scholar]
  7. Bendsen NT, Christensen R, Bartels EM, Astrup A. 7.  2011. Consumption of industrial and ruminant trans fatty acids and risk of coronary heart disease: a systematic review and meta-analysis of cohort studies. Eur. J. Clin. Nutr. 65:773–83 [Google Scholar]
  8. Briscoe CP, Peat AJ, McKeown SC, Corbett DF, Goetz AS. 8.  et al. 2006. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br. J. Pharmacol. 148:619–28 [Google Scholar]
  9. Briscoe CP, Tadayyon M, Andrews JL, Benson WG, Chambers JK. 9.  et al. 2003. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J. Biol. Chem. 278:11303–11 [Google Scholar]
  10. Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L. 10.  et al. 2003. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278:11312–19 [Google Scholar]
  11. Burant CF, Viswanathan P, Marcinak J, Cao C, Vakilynejad M. 11.  et al. 2012. TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 379:1403–11 [Google Scholar]
  12. Calder PC. 12.  2007. Dietary arachidonic acid: harmful, harmless or helpful?. Br. J. Nutr. 98:451–53 [Google Scholar]
  13. Calder PC. 13.  2012. The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability. Mol. Nutr. Food Res. 56:1073–80 [Google Scholar]
  14. Calder PC. 14.  2014. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim. Biophys. Acta 1851:469–84 [Google Scholar]
  15. Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS. 15.  2008. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 134:933–44 [Google Scholar]
  16. Cartoni C, Yasumatsu K, Ohkuri T, Shigemura N, Yoshida R. 16.  et al. 2010. Taste preference for fatty acids is mediated by GPR40 and GPR120. J. Neurosci. 30:8376–82 [Google Scholar]
  17. Chao CY, Lii CK, Ye SY, Li CC, Lu CY. 17.  et al. 2014. Docosahexaenoic acid inhibits vascular endothelial growth factor (VEGF)-induced cell migration via the GPR120/PP2A/ERK1/2/eNOS signaling pathway in human umbilical vein endothelial cells. J. Agric. Food Chem. 62:4152–58 [Google Scholar]
  18. Christiansen E, Watterson KR, Stocker CJ, Sokol E, Jenkins L. 18.  et al. 2015. Activity of dietary fatty acids on FFA1 and FFA4 and characterization of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases. Br. J. Nutr. doi: 10.1017/S000711451500118X [Google Scholar]
  19. Cintra DE, Ropelle ER, Moraes JC, Pauli JR, Morari J. 19.  et al. 2012. Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity. PLOS ONE 7:e30571 [Google Scholar]
  20. Conquer JA, Holub BJ. 20.  1998. Effect of supplementation with different doses of DHA on the levels of circulating DHA as non-esterified fatty acid in subjects of Asian Indian background. J. Lipid Res. 39:286–92 [Google Scholar]
  21. Cornall LM, Mathai ML, Hryciw DH, McAinch AJ. 21.  2011. Diet-induced obesity up-regulates the abundance of GPR43 and GPR120 in a tissue specific manner. Cell Physiol. Biochem. 28:949–58 [Google Scholar]
  22. Cornish J, MacGibbon A, Lin JM, Watson M, Callon KE. 22.  et al. 2008. Modulation of osteoclastogenesis by fatty acids. Endocrinology 149:5688–95 [Google Scholar]
  23. Davenport AP, Alexander SPH, Sharman JL, Pawson AJ, Benson HE. 23.  et al. 2013. International union of basic and clinical pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol. Rev. 65:967–86 [Google Scholar]
  24. Day JW, Ottaway N, Patterson JT, Gelfanov V, Smiley D. 24.  et al. 2009. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat. Chem. Biol. 5:749–57 [Google Scholar]
  25. Dilzer A, Park Y. 25.  2012. Implication of conjugated linoleic acid (CLA) in human health. Crit. Rev. Food Sci. Nutr. 52:488–513 [Google Scholar]
  26. Donath MY, Shoelson SE. 26.  2011. Type 2 diabetes as an inflammatory disease. Nat. Rev. Immunol. 11:98–107 [Google Scholar]
  27. Dranse HJ, Kelly MEM, Hudson BD. 27.  2013. Drugs or diet? Developing novel therapeutic strategies targeting the free fatty acid family of GPCRs. Br. J. Pharmacol. 170:696–711 [Google Scholar]
  28. Edfalk S, Steneberg P, Edlund H. 28.  2008. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 57:2280–87 [Google Scholar]
  29. Engelstoft MS, Park WM, Sakata I, Kristensen LV, Husted AS. 29.  et al. 2013. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Mol. Metab. 2:376–92 [Google Scholar]
  30. Fodor JG, Helis E, Yazdekhasti N, Vohnout B. 30.  2014. “Fishing” for the origins of the “Eskimos and heart disease” story: facts or wishful thinking?. Can. J. Cardiol. 30:864–68 [Google Scholar]
  31. Folcik VA, Cathcart MK. 31.  1994. Predominance of esterified hydroperoxy-linoleic acid in human monocyte-oxidized LDL. J. Lipid Res. 35:1570–82 [Google Scholar]
  32. Forbes JM, Cooper ME. 32.  2013. Mechanisms of diabetic complications. Physiol. Rev. 93:137–88 [Google Scholar]
  33. Fredriksson R, Hoglund PJ, Gloriam DE, Lagerstrom MC, Schioth HB. 33.  2003. Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives. FEBS Lett. 554:381–88 [Google Scholar]
  34. Galindo MM, Voigt N, Stein J, van Lengerich J, Raguse JD. 34.  et al. 2012. G protein-coupled receptors in human fat taste perception. Chem. Senses 37:123–39 [Google Scholar]
  35. Gault VA, Bhat VK, Irwin N, Flatt PR. 35.  2013. A novel glucagon-like peptide-1 (GLP-1)/glucagon hybrid peptide with triple-acting agonist activity at glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon receptors and therapeutic potential in high fat-fed mice. J. Biol. Chem. 288:35581–91 [Google Scholar]
  36. Gong Z, Yoshimura M, Aizawa S, Kurotani R, Zigman JM. 36.  et al. 2014. G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro. Am. J. Physiol. Endocrinol. Metab. 306:E28–35 [Google Scholar]
  37. Gotoh C, Hong YH, Iga T, Hishikawa D, Suzuki Y. 37.  et al. 2007. The regulation of adipogenesis through GPR120. Biochem. Biophys. Res. Commun. 354:591–97 [Google Scholar]
  38. Gribble FM. 38.  2012. The gut endocrine system as a coordinator of postprandial nutrient homoeostasis. Proc. Nutr. Soc. 71:456–62 [Google Scholar]
  39. Grosser T, Yu Y, Fitzgerald GA. 39.  2010. Emotion recollected in tranquility: lessons learned from the COX-2 saga. Annu. Rev. Med. 61:17–33 [Google Scholar]
  40. Hansen HS, Rosenkilde MM, Holst JJ, Schwartz TW. 40.  2012. GPR119 as a fat sensor. Trends Pharmacol. Sci. 33:374–81 [Google Scholar]
  41. Harris WS, Miller M, Tighe AP, Davidson MH, Schaefer EJ. 41.  2008. Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis 197:12–24 [Google Scholar]
  42. Hauge M, Vestmar MA, Husted AS, Ekberg JP, Wright MJ. 42.  et al. 2015. GPR40 (FFAR1)—combined Gs and Gq signaling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo. Mol. Metab. 4:3–14 [Google Scholar]
  43. Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T. 43.  et al. 2005. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat. Med. 11:90–94 [Google Scholar]
  44. Horrobin DF. 44.  1992. Nutritional and medicinal importance of gamma-linolenic acid. Prog. Lipid Res. 31:163–94 [Google Scholar]
  45. Hotamisligil GS. 45.  2006. Inflammation and metabolic disorders. Nature 444:860–67 [Google Scholar]
  46. Hudson BD, Shimpukade B, Mackenzie AE, Butcher AJ, Pediani JD. 46.  et al. 2013. The pharmacology of TUG-891, a potent and selective agonist of the free fatty acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and possible challenges to therapeutic agonism. Mol. Pharmacol. 84:710–25 [Google Scholar]
  47. Hudson BD, Shimpukade B, Milligan G, Ulven T. 47.  2014. The molecular basis of ligand interaction at free fatty acid receptor 4 (FFA4/GPR120). J. Biol. Chem. 289:20345–58 [Google Scholar]
  48. Ichimura A, Hirasawa A, Poulain-Godefroy O, Bonnefond A, Hara T. 48.  et al. 2012. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature 483:350–54 [Google Scholar]
  49. Imig JD. 49.  2012. Epoxides and soluble epoxide hydrolase in cardiovascular physiology. Physiol. Rev. 92:101–30 [Google Scholar]
  50. Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R. 50.  et al. 2003. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 422:173–76 [Google Scholar]
  51. Johnson GH, Fritsche K. 51.  2012. Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials. J. Acad. Nutr. Diet. 112:1029–41.e15 [Google Scholar]
  52. Kallio H, Yang B, Peippo P, Tahvonen R, Pan R. 52.  2002. Triacylglycerols, glycerophospholipids, tocopherols, and tocotrienols in berries and seeds of two subspecies (ssp. sinensis and mongolica) of Sea Buckthorn (Hippophae rhamnoides). J. Agric. Food Chem. 50:3004–9 [Google Scholar]
  53. Karpe F, Dickmann JR, Frayn KN. 53.  2011. Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes 60:2441–49 [Google Scholar]
  54. Katsuma S, Hatae N, Yano T, Ruike Y, Kimura M. 54.  et al. 2005. Free fatty acids inhibit serum deprivation-induced apoptosis through GPR120 in a murine enteroendocrine cell line STC-1. J. Biol. Chem. 280:19507–15 [Google Scholar]
  55. Kennedy A, Martinez K, Schmidt S, Mandrup S, LaPoint K, McIntosh M. 55.  2010. Antiobesity mechanisms of action of conjugated linoleic acid. J. Nutr. Biochem. 21:171–79 [Google Scholar]
  56. Kleinbongard P, Heusch G, Schulz R. 56.  2010. TNFα in atherosclerosis, myocardial ischemia/reperfusion and heart failure. Pharmacol. Ther. 127:295–314 [Google Scholar]
  57. Koren N, Simsa-Maziel S, Shahar R, Schwartz B, Monsonego-Ornan E. 57.  2014. Exposure to omega-3 fatty acids at early age accelerate bone growth and improve bone quality. J. Nutr. Biochem. 25:623–33 [Google Scholar]
  58. Korotkova M, Lundberg IE. 58.  2014. The skeletal muscle arachidonic acid cascade in health and inflammatory disease. Nat. Rev. Rheumatol. 10:295–303 [Google Scholar]
  59. Kotarsky K, Nilsson NE, Flodgren E, Owman C, Olde B. 59.  2003. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs. Biochem. Biophys. Res. Commun. 301:406–10 [Google Scholar]
  60. Le Poul E, Loison C, Struyf S, Springael JY, Lannoy V. 60.  et al. 2003. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278:25481–89 [Google Scholar]
  61. Lehtonen HM, Jarvinen R, Linderborg K, Viitanen M, Venojarvi M. 61.  et al. 2010. Postprandial hyperglycemia and insulin response are affected by sea buckthorn (Hippophae rhamnoides ssp. turkestanica) berry and its ethanol-soluble metabolites. Eur. J. Clin. Nutr. 64:1465–71 [Google Scholar]
  62. Lehtonen HM, Suomela JP, Tahvonen R, Yang B, Venojarvi M. 62.  et al. 2011. Different berries and berry fractions have various but slightly positive effects on the associated variables of metabolic diseases on overweight and obese women. Eur. J. Clin. Nutr. 65:394–401 [Google Scholar]
  63. Li X, Yu Y, Funk CD. 63.  2013. Cyclooxygenase-2 induction in macrophages is modulated by docosahexaenoic acid via interactions with free fatty acid receptor 4 (FFA4). FASEB J. 27:4987–97 [Google Scholar]
  64. Li Y, Zhang H, Jiang C, Xu M, Pang Y. 64.  et al. 2013. Hyperhomocysteinemia promotes insulin resistance by inducing endoplasmic reticulum stress in adipose tissue. J. Biol. Chem. 288:9583–92 [Google Scholar]
  65. Liou AP, Lu X, Sei Y, Zhao X, Pechhold S. 65.  et al. 2011. The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin. Gastroenterology 140:903–12 [Google Scholar]
  66. Little TJ, Isaacs NJ, Young RL, Ott R, Nguyen NQ. 66.  et al. 2014. Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index. Am. J. Physiol. Gastrointest. Liver Physiol. 307G958–67 [Google Scholar]
  67. Liu D, Wang L, Meng Q, Kuang H, Liu X. 66.  2012. G-protein coupled receptor 120 is involved in glucose metabolism in fat cells. Cell. Mol. Biol 58OL1757–62 [Google Scholar]
  68. Liu Y, Chen LY, Sokolowska M, Eberlein M, Alsaaty S. 68.  et al. 2014. 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 143:81–95 [Google Scholar]
  69. Lu X, Zhao X, Feng J, Liou AP, Anthony S. 69.  et al. 2012. Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice. Am. J. Physiol. Gastrointest. Liver Physiol. 303:G367–76 [Google Scholar]
  70. Lumeng CN, Saltiel AR. 70.  2011. Inflammatory links between obesity and metabolic disease. J. Clin. Invest. 121:2111–17 [Google Scholar]
  71. Luo J, Swaminath G, Brown SP, Zhang J, Guo Q. 71.  et al. 2012. A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents. PLOS ONE 7:e46300 [Google Scholar]
  72. Luo P, Wang MH. 72.  2011. Eicosanoids, β-cell function, and diabetes. Prostaglandins Other Lipid Mediat. 95:1–10 [Google Scholar]
  73. Ma J, Checklin HL, Wishart JM, Stevens JE, Jones KL. 73.  et al. 2013. A randomised trial of enteric-coated nutrient pellets to stimulate gastrointestinal peptide release and lower glycaemia in type 2 diabetes. Diabetologia 56:1236–42 [Google Scholar]
  74. Madsbad S, Dirksen C, Holst JJ. 74.  2014. Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery. Lancet Diabetes Endocrinol. 2:152–64 [Google Scholar]
  75. Martin C, Chevrot M, Poirier H, Passilly-Degrace P, Niot I, Besnard P. 75.  2011. CD36 as a lipid sensor. Physiol. Behav. 105:36–42 [Google Scholar]
  76. Martin C, Passilly-Degrace P, Chevrot M, Ancel D, Sparks SM. 76.  et al. 2012. 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. 53:2256–65 [Google Scholar]
  77. Martinez JA, Navas-Carretero S, Saris WH, Astrup A. 77.  2014. Personalized weight loss strategies—the role of macronutrient distribution. Nat. Rev. Endocrinol. 10:749–60 [Google Scholar]
  78. Marzuillo P, Grandone A, Conte M, Capuano F, Cirillo G. 78.  et al. 2014. 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. 59:472–75 [Google Scholar]
  79. Matsumura S, Eguchi A, Mizushige T, Kitabayashi N, Tsuzuki S. 79.  et al. 2009. Colocalization of GPR120 with phospholipase-Cβ2 and α-gustducin in the taste bud cells in mice. Neurosci. Lett. 450:186–90 [Google Scholar]
  80. Micallef M, Munro I, Phang M, Garg M. 80.  2009. Plasma n-3 polyunsaturated fatty acids are negatively associated with obesity. Br. J. Nutr. 102:1370–74 [Google Scholar]
  81. Micha R, Mozaffarian D. 81.  2009. Trans fatty acids: effects on metabolic syndrome, heart disease and diabetes. Nat. Rev. Endocrinol. 5:335–44 [Google Scholar]
  82. Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK. 82.  et al. 2006. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol. Rev. 58:726–41 [Google Scholar]
  83. Milligan G, Ulven T, Murdoch H, Hudson BD. 83.  2014. G-protein-coupled receptors for free fatty acids: nutritional and therapeutic targets. Br. J. Nutr. 111:S3–7 [Google Scholar]
  84. Miyauchi S, Hirasawa A, Iga T, Liu N, Itsubo C. 84.  et al. 2009. Distribution and regulation of protein expression of the free fatty acid receptor GPR120. Naunyn-Schmiedeberg's Arch. Pharmacol. 379:427–34 [Google Scholar]
  85. Moore K, Zhang Q, Murgolo N, Hosted T, Duffy R. 85.  2009. 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. 154:419–26 [Google Scholar]
  86. Morishita M, Tanaka T, Shida T, Takayama K. 86.  2008. Usefulness of colon targeted DHA and EPA as novel diabetes medications that promote intrinsic GLP-1 secretion. J. Control. Release 132:99–104 [Google Scholar]
  87. Mu H, Porsgaard T. 87.  2005. The metabolism of structured triacylglycerols. Prog. Lipid Res. 44:430–48 [Google Scholar]
  88. Nilsson NE, Kotarsky K, Owman C, Olde B. 88.  2003. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem. Biophys. Res. Commun. 303:1047–52 [Google Scholar]
  89. Nobili V, Carpino G, Alisi A, De Vito R, Franchitto A. 89.  et al. 2014. Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease. PLOS ONE 9:e88005 [Google Scholar]
  90. Nording ML, Yang J, Georgi K, Hegedus Karbowski C, German JB. 90.  et al. 2013. Individual variation in lipidomic profiles of healthy subjects in response to omega-3 fatty acids. PLOS ONE 8:e76575 [Google Scholar]
  91. Oh da Y, Walenta E, Akiyama TE, Lagakos WS, Lackey D. 91.  et al. 2014. A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nat. Med. 20:942–47 [Google Scholar]
  92. Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H. 92.  et al. 2010. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142:687–98 [Google Scholar]
  93. Olefsky JM, Glass CK. 93.  2010. Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol. 72:219–46 [Google Scholar]
  94. Ozdener MH, Subramaniam S, Sundaresan S, Sery O, Hashimoto T. 94.  et al. 2014. CD36- and GPR120-mediated Ca2+ signaling in human taste bud cells mediates differential responses to fatty acids and is altered in obese mice. Gastroenterology 146:995–1005 [Google Scholar]
  95. Parker HE, Habib AM, Rogers GJ, Gribble FM, Reimann F. 95.  2009. Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells. Diabetologia 52:289–98 [Google Scholar]
  96. Pasman WJ, Heimerikx J, Rubingh CM, van den Berg R, O'Shea M. 96.  et al. 2008. The effect of Korean pine nut oil on in vitro CCK release, on appetite sensations and on gut hormones in post-menopausal overweight women. Lipids Health Dis. 7:10 [Google Scholar]
  97. Paulsen SJ, Larsen LK, Hansen G, Chelur S, Larsen PJ, Vrang N. 97.  2014. Expression of the fatty acid receptor GPR120 in the gut of diet-induced-obese rats and its role in GLP-1 secretion. PLOS ONE 9:e88227 [Google Scholar]
  98. Pocai A, Carrington PE, Adams JR, Wright M, Eiermann G. 98.  et al. 2009. Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice. Diabetes 58:2258–66 [Google Scholar]
  99. Raptis DA, Limani P, Jang JH, Ungethum U, Tschuor C. 99.  et al. 2014. GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids. J. Hepatol. 60:625–32 [Google Scholar]
  100. Rodriguez-Pacheco F, Garcia-Serrano S, Garcia-Escobar E, Gutierrez-Repiso C, Garcia-Arnes J. 100.  et al. 2014. Effects of obesity/fatty acids on the expression of GPR120. Mol. Nutr. Food Res. 58:1852–60 [Google Scholar]
  101. Rosell M, Kaforou M, Frontini A, Okolo A, Chan Y-W. 101.  et al. 2014. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice. Am. J. Physiol. Endocrinol. Metab. 306:E945–64 [Google Scholar]
  102. Sadry SA, Drucker DJ. 102.  2013. Emerging combinatorial hormone therapies for the treatment of obesity and T2DM. Nat. Rev. Endocrinol. 9:425–33 [Google Scholar]
  103. Scher JU, Pillinger MH. 103.  2009. The anti-inflammatory effects of prostaglandins. J. Invest. Med. 57:703–8 [Google Scholar]
  104. Schmidt J, Liebscher K, Merten N, Grundmann M, Mielenz M. 104.  et al. 2011. Conjugated linoleic acids mediate insulin release through islet G protein-coupled receptor FFA1/GPR40. J. Biol. Chem. 286:11890–94 [Google Scholar]
  105. Schuchardt JP, Hahn A. 105.  2013. Bioavailability of long-chain omega-3 fatty acids. Prostaglandins Leukot. Essent. Fatty Acids 89:1–8 [Google Scholar]
  106. Scorletti E, Byrne CD. 105.  2013. Omega-3 fatty acids, hepatic lipid metabolism, and nonalcoholic fatty liver disease. Annu. Rev. Nutr. 33:231–48 [Google Scholar]
  107. Serhan CN. 106.  2014. Pro-resolving lipid mediators are leads for resolution physiology. Nature 510:92–101 [Google Scholar]
  108. Serhan CN, Petasis NA. 107.  2011. Resolvins and protectins in inflammation resolution. Chem. Rev. 111:5922–43 [Google Scholar]
  109. Shimpukade B, Hudson BD, Hovgaard CK, Milligan G, Ulven T. 108.  2012. Discovery of a potent and selective GPR120 agonist. J. Med. Chem. 55:4511–15 [Google Scholar]
  110. Sparks SM, Chen G, Collins JL, Danger D, Dock ST. 109.  et al. 2014. Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120). Bioorg. Med. Chem. Lett. 24:3100–3 [Google Scholar]
  111. Stoddart LA, Smith NJ, Milligan G. 110.  2008. International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions. Pharmacol. Rev. 60:405–17 [Google Scholar]
  112. Stone VM, Dhayal S, Brocklehurst KJ, Lenaghan C, Sorhede Winzell M. 111.  et al. 2014. GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans. Diabetologia 57:1182–91 [Google Scholar]
  113. Suckow AT, Polidori D, Yan W, Chon S, Ma JY. 112.  et al. 2014. Alteration of the glucagon axis in GPR120 (FFAR4) knockout mice: a role for GPR120 in glucagon secretion. J. Biol. Chem. 289:15751–63 [Google Scholar]
  114. Suzuki T, Igari SI, Hirasawa A, Hata M, Ishiguro M. 113.  et al. 2008. Identification of G protein-coupled receptor 120-selective agonists derived from PPARγ agonists. J. Med. Chem. 51:7640–44 [Google Scholar]
  115. Sykaras AG, Demenis C, Case RM, McLaughlin JT, Smith CP. 114.  2012. Duodenal enteroendocrine I-cells contain mRNA transcripts encoding key endocannabinoid and fatty acid receptors. PLOS ONE 7:e42373 [Google Scholar]
  116. Talukdar S, Olefsky JM, Osborn O. 115.  2011. Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases. Trends Pharmacol. Sci. 32:543–50 [Google Scholar]
  117. Tam CS, Berthoud HR, Bueter M, Chakravarthy MV, Geliebter A. 116.  et al. 2011. Could the mechanisms of bariatric surgery hold the key for novel therapies? Report from a Pennington Scientific Symposium. Obes. Rev. 12:984–94 [Google Scholar]
  118. Tanaka T, Katsuma S, Adachi T, Koshimizu TA, Hirasawa A, Tsujimoto G. 117.  2008. Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn Schmiedebergs Arch. Pharmacol. 377:523–27 [Google Scholar]
  119. Taneera J, Lang S, Sharma A, Fadista J, Zhou Y. 118.  et al. 2012. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets. Cell Metab. 16:122–34 [Google Scholar]
  120. Tomita T, Hosoda K, Fujikura J, Inagaki N, Nakao K. 118a.  2014. The G-protein-coupled long-chain fatty acid receptor GPR40 and glucose metabolism. Front. Endocrinol. 5:152 [Google Scholar]
  121. Turgeon SL, Rioux L-E. 119.  2011. Food matrix impact on macronutrients nutritional properties. Food Hydrocolloids 25:1915–24 [Google Scholar]
  122. Ulven T. 120.  2012. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Front. Endocrinol. 3:111 [Google Scholar]
  123. van der Wielen N, van Avesaat M, de Wit NJ, Vogels JT, Troost F. 121.  et al. 2014. Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine. PLOS ONE 9:e107531 [Google Scholar]
  124. Vannice G, Rasmussen H. 122.  2014. Position of the Academy of Nutrition and Dietetics: dietary fatty acids for healthy adults. J. Acad. Nutr. Diet. 114:136–53 [Google Scholar]
  125. Virtanen JK, Mursu J, Voutilainen S, Uusitupa M, Tuomainen TP. 123.  2014. Serum omega-3 polyunsaturated fatty acids and risk of incident type 2 diabetes in men: the Kuopio Ischemic Heart Disease Risk Factor Study. Diabetes Care 37:189–96 [Google Scholar]
  126. Wagner R, Kaiser G, Gerst F, Christiansen E, Due-Hansen ME. 124.  et al. 2013. Reevaluation of fatty acid receptor 1 as a drug target for the stimulation of insulin secretion in humans. Diabetes 62:2106–11 [Google Scholar]
  127. Waguri T, Goda T, Kasezawa N, Yamakawa-Kobayashi K. 125.  2013. The combined effects of genetic variations in the GPR120 gene and dietary fat intake on obesity risk. Biomed. Res. 34:69–74 [Google Scholar]
  128. Walker CG, Jebb SA, Calder PC. 126.  2013. Stearidonic acid as a supplemental source of omega-3 polyunsaturated fatty acids to enhance status for improved human health. Nutrition 29:363–69 [Google Scholar]
  129. Wang JH, Wu XS, Simonavicius N, Tian H, Ling L. 127.  2006. Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J. Biol. Chem. 281:34457–64 [Google Scholar]
  130. Watson SJ, Brown AJ, Holliday ND. 128.  2012. Differential signaling by splice variants of the human free fatty acid receptor GPR120. Mol. Pharmacol. 81:631–42 [Google Scholar]
  131. Watterson KR, Hudson BD, Ulven T, Milligan G. 129.  2014. Treatment of type 2 diabetes by free fatty acid receptor agonists. Front. Endocrinol. 5:137 [Google Scholar]
  132. Wellhauser L, Belsham DD. 130.  2014. Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons. J. Neuroinflammation 11:60 [Google Scholar]
  133. Widmayer P, Kuper M, Kramer M, Konigsrainer A, Breer H. 131.  2012. Altered expression of gustatory-signaling elements in gastric tissue of morbidly obese patients. Int. J. Obes. 36:1353–59 [Google Scholar]
  134. Willett WC, Stampfer MJ. 132.  2013. Current evidence on healthy eating. Annu. Rev. Public Health 34:77–95 [Google Scholar]
  135. Williams-Bey Y, Boularan C, Vural A, Huang NN, Hwang IY. 133.  et al. 2014. Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-κB activation and enhancing autophagy. PLOS ONE 9:e97957 [Google Scholar]
  136. Woodward DF, Jones RL, Narumiya S. 134.  2011. International Union of Basic and Clinical Pharmacology. LXXXIII: classification of prostanoid receptors, updating 15 years of progress. Pharmacol. Rev. 63:471–538 [Google Scholar]
  137. Wu JH, Micha R, Imamura F, Pan A, Biggs ML. 135.  et al. 2012. Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis. Br. J. Nutr. 107:Suppl. 2S214–27 [Google Scholar]
  138. Xu H, Barnes GT, Yang Q, Tan G, Yang D. 136.  et al. 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112:1821–30 [Google Scholar]
  139. Yan Y, Jiang W, Spinetti T, Tardivel A, Castillo R. 137.  et al. 2013. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity 38:1154–63 [Google Scholar]
  140. Yanai H, Hamasaki H, Katsuyama H, Adachi H, Moriyama S, Sako A. 138.  2015. Effects of intake of fish or fish oils on the development of diabetes. J. Clin. Med. Res. 7:8–12 [Google Scholar]
  141. Yin J, Zhang H, Ye J. 139.  2008. Traditional Chinese medicine in treatment of metabolic syndrome. Endocr. Metab. Immune Disord. Drug Targets 8:99–111 [Google Scholar]
  142. Yore MM, Syed I, Moraes-Vieira PM, Zhang T, Herman MA. 140.  et al. 2014. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159:318–32 [Google Scholar]
  143. Zhang Y, Xu MT, Zhang SL, Yan L, Yang C. 141.  et al. 2007. The role of G protein-coupled receptor 40 in lipoapoptosis in mouse beta-cell line NIT-1. J. Mol. Endocrinol. 38:651–61 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error