About this Journal Submit a Manuscript Table of Contents
Journal of Nutrition and Metabolism
Volume 2012 (2012), Article ID 539426, 16 pages
http://dx.doi.org/10.1155/2012/539426
Review Article

Health Implications of High Dietary Omega-6 Polyunsaturated Fatty Acids

1Alimentary Pharmabiotic Centre, Biosciences Institute, County Cork, Ireland
2Teagasc Food Research Centre, Biosciences Department, Moorepark, Fermoy, County Cork, Ireland
3Department of Microbiology, University College Cork, County Cork, Ireland

Received 28 July 2011; Revised 17 November 2011; Accepted 20 November 2011

Academic Editor: Rémy Meier

Copyright © 2012 E. Patterson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. C. Calder, “Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases,” Molecular Nutrition and Food Research, vol. 52, no. 8, pp. 885–897, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. R. Wall, R. P. Ross, G. F. Fitzgerald, and C. Stanton, “Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids,” Nutrition Reviews, vol. 68, no. 5, pp. 280–289, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. P. C. Calder, “Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale,” Biochimie, vol. 91, no. 6, pp. 791–795, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. M. C. Olivier, L. Vanessa, and A. Isabelle, “Why and how meet n-3 PUFA dietary recommendations?” Gastroenterology Research and Practice, vol. 2011, Article ID 364040, 11 pages, 2011. View at Publisher · View at Google Scholar · View at PubMed
  5. A. P. Simopoulos, “Evolutionary aspects of Diet: the omega-6/omega-3 ratio and the brain,” Molecular Neurobiology, vol. 44, no. 3, pp. 203–215, 2011. View at Publisher · View at Google Scholar
  6. J. Linseisen, A. A. Welch, M. Ocké et al., “Dietary fat intake in the European Prospective Investigation into Cancer and Nutrition: results from the 24-h dietary recalls,” European Journal of Clinical Nutrition, vol. 63, no. 4, pp. S61–S80, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. S. B. Eaton, M. J. Konner, and L. Cordain, “Diet-dependent acid load, Paleolithic nutrition, and evolutionary health promotion,” The American Journal of Clinical Nutrition, vol. 91, no. 2, pp. 295–297, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. A. P. Simopoulos, “N-3 fatty acids and human health: defining strategies for public policy,” Lipids, vol. 36, pp. S83–S89, 2001. View at Scopus
  9. B. M. Anderson and D. Ma, “Are all n-3 polyunsaturated fatty acids created equal?” Lipids in Health and Disease, vol. 8, no. 1, article 33, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. L. Corsinovi, F. Biasi, G. Poli, G. Leonarduzzi, and G. Isaia, “Dietary lipids and their oxidized products in Alzheimer's disease,” Molecular Nutrition and Food Research, vol. 55, supplement 2, pp. S161–S172, 2011. View at Publisher · View at Google Scholar
  11. S. T. B. S. Hassan and P. Hanachi, “Dietary patterns and the metabolic syndrome in middle aged women, Babol, Iran,” Asia Pacific Journal of Clinical Nutrition, vol. 18, no. 2, pp. 285–292, 2009. View at Scopus
  12. J. B. Ruidavets, V. Bongard, J. Dallongeville et al., “High consumptions of grain, fish, dairy products and combinations of these are associated with a low prevalence of metabolic syndrome,” Journal of Epidemiology and Community Health, vol. 61, no. 9, pp. 810–817, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. U. N. Das, “Essential fatty acids: biochemistry, physiology and pathology,” Biotechnology Journal, vol. 1, no. 4, pp. 420–439, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. C. L. Hughes and T. R. Dhiman, “Dietary compounds in relation to dietary diversity and human health,” Journal of Medicinal Food, vol. 5, no. 2, pp. 51–68, 2002. View at Scopus
  15. R. Uauy and A. D. Dangour, “Nutrition in brain development and aging: role of essential fatty acids,” Nutrition Reviews, vol. 64, no. 5, pp. S24–S33, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. F. Lauretani, R. D. Semba, S. Bandinelli et al., “Plasma polyunsaturated fatty acids and the decline of renal function,” Clinical Chemistry, vol. 54, no. 3, pp. 475–481, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. A. M. El-Badry, R. Graf, and P. A. Clavien, “Omega 3—omega 6: what is right for the liver?” Journal of Hepatology, vol. 47, no. 5, pp. 718–725, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. P. Benatti, G. Peluso, R. Nicolai, and M. Calvani, “Polyunsaturated fatty acids: biochemical, nutritional and epigenetic properties,” Journal of the American College of Nutrition, vol. 23, no. 4, pp. 281–302, 2004. View at Scopus
  19. W. Stoffel, B. Holz, B. Jenke et al., “Δ6-Desaturase (FADS2) deficiency unveils the role of ω3- and ω6-polyunsaturated fatty acids,” The EMBO Journal, vol. 27, no. 17, pp. 2281–2292, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. Y. A. Moon, R. E. Hammer, and J. D. Horton, “Deletion of ELOVL5 leads to fatty liver through activation of SREBP-1c in mice,” Journal of Lipid Research, vol. 50, no. 3, pp. 412–423, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. G. Schmitz and J. Ecker, “The opposing effects of n-3 and n-6 fatty acids,” Progress in Lipid Research, vol. 47, no. 2, pp. 147–155, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. C. K. Stroud, T. Y. Nara, M. Roqueta-Rivera et al., “Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration,” Journal of Lipid Research, vol. 50, no. 9, pp. 1870–1880, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Araya, R. Rodrigo, P. Pettinelli, A. V. Araya, J. Poniachik, and L. A. Videla, “Decreased liver fatty Acid delta-6 and delta-5 desaturase activity in obese patients,” Obesity, vol. 18, no. 7, pp. 1460–1463, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. R. R. Brenner, “Hormonal modulation of delta6 and delta5 desaturases: case of diabetes,” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 68, no. 2, pp. 151–162, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. R. R. Brenner, “Nutritional and hormonal factors influencing desaturation of essential fatty acids,” Progress in Lipid Research, vol. 20, pp. 41–47, 1981. View at Scopus
  26. U. N. Das, “Biological significance of essential fatty acids,” Journal of Association of Physicians of India, vol. 54, pp. 309–319, 2006. View at Scopus
  27. A. P. Simopoulos, “Omega-3 fatty acids in inflammation and autoimmune diseases,” Journal of the American College of Nutrition, vol. 21, no. 6, pp. 495–505, 2002. View at Scopus
  28. D. Zadravec, P. Tvrdik, H. Guillou et al., “ELOVL2 controls the level of n-6 28:5 and 30:5 fatty acids in testis, a prerequisite for male fertility and sperm maturation in mice,” Journal of Lipid Research, vol. 52, no. 2, pp. 245–255, 2011. View at Publisher · View at Google Scholar
  29. G. L. Russo, “Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention,” Biochemical Pharmacology, vol. 77, no. 6, pp. 937–946, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. D. Wang and R. N. Dubois, “Eicosanoids and cancer,” Nature Reviews Cancer, vol. 10, no. 3, pp. 181–193, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. E. Ricciotti and G. A. Fitzgerald, “Prostaglandins and inflammation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 5, pp. 986–1000, 2011. View at Publisher · View at Google Scholar · View at PubMed
  32. C. C. Tai and S. T. Ding, “N-3 polyunsaturated fatty acids regulate lipid metabolism through several inflammation mediators: mechanisms and implications for obesity prevention,” Journal of Nutritional Biochemistry, vol. 21, no. 5, pp. 357–363, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. J. de Batlle, et al., “Association between [Omega] 3 and [Omega] 6 fatty acid intakes and serum inflammatory markers in COPD,” The Journal of Nutritional Biochemistry. In press.
  34. K. Poudel-Tandukar, A. Nanri, Y. Matsushita et al., “Dietary intakes of α-linolenic and linoleic acids are inversely associated with serum C-reactive protein levels among Japanese men,” Nutrition Research, vol. 29, no. 6, pp. 363–370, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. S. Yoneyama, K. Miura, S. Sasaki et al., “Dietary intake of fatty acids and serum C-reactive protein in Japanese,” Journal of Epidemiology, vol. 17, no. 3, pp. 86–92, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. K. L. Fritsche, “Too much linoleic acid promotes inflammation—doesn't it?” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 79, no. 3–5, pp. 173–175, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. H. Harizi, J. B. Corcuff, and N. Gualde, “Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology,” Trends in Molecular Medicine, vol. 14, no. 10, pp. 461–469, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. N. G. Bazan, “Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection,” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 81, no. 2-3, pp. 205–211, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. G. Fredman and C. N. Serhan, “Specialized proresolving mediator targets for RvE1 and RvD1 in peripheral blood and mechanisms of resolution,” The Biochemical Journal, vol. 437, no. 2, pp. 185–197, 2011. View at Publisher · View at Google Scholar
  40. G. Levin, K. L. Duffin, M. G. Obukowicz et al., “Differential metabolism of dihomo-γ-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E-1 and prostaglandin E-2,” Biochemical Journal, vol. 365, no. 2, pp. 489–496, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. D. Bagga, L. Wang, R. Farias-Eisner, J. A. Glaspy, and S. T. Reddy, “Differential effects of prostaglandin derived from ω-6 and ω-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 4, pp. 1751–1756, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. A. M. Pulichino, S. Rowland, T. Wu et al., “Prostacyclin antagonism reduces pain and inflammation in rodent models of hyperalgesia and chronic arthritis,” Journal of Pharmacology and Experimental Therapeutics, vol. 319, no. 3, pp. 1043–1050, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. F. Kojima, S. Kato, and S. Kawai, “Prostaglandin E synthase in the pathophysiology of arthritis,” Fundamental and Clinical Pharmacology, vol. 19, no. 3, pp. 255–261, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. S. L. Tilley, T. M. Coffman, and B. H. Koller, “Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes,” Journal of Clinical Investigation, vol. 108, no. 1, pp. 15–23, 2001. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Peters-Golden and W. R. Henderson Jr., “Leukotrienes,” New England Journal of Medicine, vol. 357, no. 18, pp. 1841–1854, 2007.
  46. J. G. Robinson and N. J. Stone, “Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids,” American Journal of Cardiology, vol. 98, no. 4, pp. 39–49, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. A. N. Hata and R. M. Breyer, “Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation,” Pharmacology and Therapeutics, vol. 103, no. 2, pp. 147–166, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. S. Narumiya and G. A. FitzGerald, “Genetic and pharmacological analysis of prostanoid receptor function,” Journal of Clinical Investigation, vol. 108, no. 1, pp. 25–30, 2001. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Ide, K. Egan, L. C. Bell-Parikh, and G. A. FitzGerald, “Activation of nuclear receptors by prostaglandins,” Thrombosis Research, vol. 110, no. 5-6, pp. 311–315, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Arima and T. Fukuda, “Prostaglandin D2 and TH2 inflammation in the pathogenesis of bronchial asthma,” The Korean Journal of Internal Medicine, vol. 26, no. 1, pp. 8–18, 2011. View at Publisher · View at Google Scholar
  51. R. Pettipher, T. T. Hansel, and R. Armer, “Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases,” Nature Reviews Drug Discovery, vol. 6, no. 4, pp. 313–325, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. K. A. Lundeen, B. Sun, L. Karlsson, and A. M. Fourie, “Leukotriene B4 receptors BLT1 and BLT2: expression and function in human and murine mast cells,” Journal of Immunology, vol. 177, no. 5, pp. 3439–3447, 2006. View at Scopus
  53. J. Jupp, K. Hillier, D. H. Elliott et al., “Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases,” Inflammatory Bowel Diseases, vol. 13, no. 5, pp. 537–546, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. C. D. Funk, “Prostaglandins and leukotrienes: advances in eicosanoid biology,” Science, vol. 294, no. 5548, pp. 1871–1875, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. C. N. Serhan and J. Savill, “Resolution of inflammation: the beginning programs the end,” Nature Immunology, vol. 6, no. 12, pp. 1191–1197, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. A. Chawla, J. J. Repa, R. M. Evans, and D. J. Mangelsdorf, “Nuclear receptors and lipid physiology: opening the X-files,” Science, vol. 294, no. 5548, pp. 1866–1870, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. S. J. Bensinger and P. Tontonoz, “Integration of metabolism and inflammation by lipid-activated nuclear receptors,” Nature, vol. 454, no. 7203, pp. 470–477, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. I. Issemann and S. Green, “Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators,” Nature, vol. 347, no. 6294, pp. 645–650, 1990. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. C. Couet, J. Delarue, P. Ritz, J. M. Antoine, and F. Lamisse, “Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults,” International Journal of Obesity, vol. 21, no. 8, pp. 637–643, 1997. View at Scopus
  60. G. W. Power and E. A. Newsholme, “Dietary fatty acids influence the activity and metabolic control of mitochondrial carnitine palmitoyltransferase I in rat heart and skeletal muscle,” Journal of Nutrition, vol. 127, no. 11, pp. 2142–2150, 1997. View at Scopus
  61. F. B. Hu, M. J. Stampfer, J. E. Manson et al., “Dietary intake of α-linolenic acid and risk of fatal ischemic heart disease among women,” American Journal of Clinical Nutrition, vol. 69, no. 5, pp. 890–897, 1999. View at Scopus
  62. T. A. Mori, D. Q. Bao, V. Burke, I. B. Puddey, G. F. Watts, and L. J. Beilin, “Dietary fish as a major component of a weight-loss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects,” American Journal of Clinical Nutrition, vol. 70, no. 5, pp. 817–825, 1999. View at Scopus
  63. M. V. Chakravarthy, I. J. Lodhi, L. Yin et al., “Identification of a physiologically relevant endogenous ligand for PPARα in liver,” Cell, vol. 138, no. 3, pp. 476–488, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. M. J. Yoon, Y. L. Gha, J. J. Chung, H. A. Young, H. H. Seung, and B. K. Jae, “Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator—activated receptorα,” Diabetes, vol. 55, no. 9, pp. 2562–2570, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. K. Fujita, N. Maeda, M. Sonoda et al., “Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPAR-α,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 5, pp. 863–870, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. N. D. Perkins, “Integrating cell-signalling pathways with NF-κB and IKK function,” Nature Reviews Molecular Cell Biology, vol. 8, no. 1, pp. 49–62, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. Y. Zhao, S. Joshi-Barve, S. Barve, and L. H. Chen, “Eicosapentaenoic acid prevents LPS-induced TNF-α expression by preventing NF-κB activation,” Journal of the American College of Nutrition, vol. 23, no. 1, pp. 71–78, 2004. View at Scopus
  68. S. M. Weldon, A. C. Mullen, C. E. Loscher, L. A. Hurley, and H. M. Roche, “Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid,” Journal of Nutritional Biochemistry, vol. 18, no. 4, pp. 250–258, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. R. de Caterina, M. Spiecker, G. Solaini et al., “The inhibition of endothelial activation by unsaturated fatty acids,” Lipids, vol. 34, no. 6, pp. S191–S194, 1999. View at Scopus
  70. R. A. Lepley and F. A. Fitzpatrick, “5-lipoxygenase compartmentalization in granulocytic cells is modulated by an internal bipartite nuclear localizing sequence and nuclear factor κB complex formation,” Archives of Biochemistry and Biophysics, vol. 356, no. 1, pp. 71–76, 1998. View at Publisher · View at Google Scholar · View at Scopus
  71. R. J. Soberman and P. Christmas, “The organization and consequences of eicosanoid signaling,” Journal of Clinical Investigation, vol. 111, no. 8, pp. 1107–1113, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. J. Ecker, T. Langmann, C. Moehle, and G. Schmitz, “Isomer specific effects of Conjugated Linoleic Acid on macrophage ABCG1 transcription by a SREBP-1c dependent mechanism,” Chemistry and Physics of Lipids, vol. 149, pp. S59–S59, 2007.
  73. J. Xu, H. Cho, S. O'Malley, J. H. Y. Park, and S. D. Clarke, “Dietary polyunsaturated fats regulate rat liver sterol regulatory element binding proteins-1 and -2 in three distinct stages and by different mechanisms,” Journal of Nutrition, vol. 132, no. 11, pp. 3333–3339, 2002. View at Scopus
  74. M. Teran-Garcia, A. W. Adamson, G. Yu et al., “Polyunsaturated fatty acid suppression of fatty acid synthase (FASN): evidence for dietary modulation of NF-Y binding to the Fasn promoter by SREBP-1c,” Biochemical Journal, vol. 402, no. 3, pp. 591–600, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  75. J. Xu, M. T. Nakamura, H. P. Cho, and S. D. Clarke, “Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats,” Journal of Biological Chemistry, vol. 274, no. 33, pp. 23577–23583, 1999. View at Publisher · View at Google Scholar · View at Scopus
  76. J. Xu, M. Teran-Garcia, J. H. Y. Park, M. T. Nakamura, and S. D. Clarke, “Polyunsaturated fatty acids suppress hepatic sterol regulatory element-binding protein-1 expression by accelerating transcript decay,” Journal of Biological Chemistry, vol. 276, no. 13, pp. 9800–9807, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  77. G. Howell III, X. Deng, C. Yellaturu et al., “N-3 polyunsaturated fatty acids suppress insulin-induced SREBP-1c transcription via reduced trans-activating capacity of LXRα,” Biochimica et Biophysica Acta: Molecular and Cell Biology of Lipids, vol. 1791, no. 12, pp. 1190–1196, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. B. D. Pachikian, A. Essaghir, J. -B. Demoulin et al., “Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets,” PLoS ONE, vol. 6, no. 8, article e23365, 2011. View at Publisher · View at Google Scholar
  79. A. Pawar, D. Botolin, D. J. Mangelsdorf, and D. B. Jump, “The role of liver X receptor-α in the fatty acid regulation of hepatic gene expression,” Journal of Biological Chemistry, vol. 278, no. 42, pp. 40736–40743, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. T. Yoshikawa, T. Ide, H. Shimano et al., “Cross-talk between peroxisome proliferator-activated receptor (PPAR) α and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARS suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling,” Molecular Endocrinology, vol. 17, no. 7, pp. 1240–1254, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. C. Byrne, R. Olufad, K. D. Bruce, F. R. Cagampang, and M. H. Ahmed, “Metabolic disturbances in non-alcoholic fatty liver disease,” Clinical Science, vol. 116, no. 7, pp. 539–564, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  82. C. D. Byrne, “Fatty liver: role of inflammation and fatty acid nutrition,” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 82, no. 4–6, pp. 265–271, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  83. S. K. Erickson, “Nonalcoholic fatty liver disease,” Journal of Lipid Research, vol. 50, supplement, pp. S412–S416, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. L. A. Videla, R. Rodrigo, J. Araya, and J. Poniachik, “Insulin resistance and oxidative stress interdependency in non-alcoholic fatty liver disease,” Trends in Molecular Medicine, vol. 12, no. 12, pp. 555–558, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  85. C. Z. Larter, M. M. Yeh, J. Cheng et al., “Activation of peroxisome proliferator-activated receptor α by dietary fish oil attenuates steatosis, but does not prevent experimental steatohepatitis because of hepatic lipoperoxide accumulation,” Journal of Gastroenterology and Hepatology, vol. 23, no. 2, pp. 267–275, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  86. J. Araya, R. Rodrigo, L. A. Videla et al., “Increase in long-chain polyunsaturated fatty acid n-6/n-3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease,” Clinical Science, vol. 106, no. 6, pp. 635–643, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  87. L. Spadaro, O. Magliocco, D. Spampinato et al., “Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease,” Digestive and Liver Disease, vol. 40, no. 3, pp. 194–199, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  88. A. M. Zivkovic, J. B. German, and A. J. Sanyal, “Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease,” American Journal of Clinical Nutrition, vol. 86, no. 2, pp. 285–300, 2007. View at Scopus
  89. D. B. Jump, “N-3 polyunsaturated fatty acid regulation of hepatic gene transcription,” Current Opinion in Lipidology, vol. 19, no. 3, pp. 242–247, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  90. E. Ip, G. Farrell, P. Hall, G. Robertson, and I. Leclercq, “Administration of the potent PPARα agonist, Wy-14,643, reverses nutritional fibrosis and steatohepatitis in mice,” Hepatology, vol. 39, no. 5, pp. 1286–1296, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  91. E. Ip, G. C. Farrell, G. Robertson, P. Hall, R. Kirsch, and I. Leclercq, “Central role of PPARα-dependent hepatic lipid turnover in dietary steatohepatitis in mice,” Hepatology, vol. 38, no. 1, pp. 123–132, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. D. Lindén, K. Lindberg, J. Oscarsson et al., “Influence of peroxisome proliferator-activated receptor α agonists on the intracellular turnover and secretion of apolipoprotein (Apo) B-100 and ApoB-48,” Journal of Biological Chemistry, vol. 277, no. 25, pp. 23044–23053, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  93. L. Carlsson, D. Lindén, M. Jalouli, and J. Oscarsson, “Effects of fatty acids and growth hormone on liver fatty acid binding protein and PPARα in rat liver,” American Journal of Physiology: Endocrinology and Metabolism, vol. 281, no. 4, pp. E772–E781, 2001. View at Scopus
  94. D. B. Savage and R. K. Semple, “Recent insights into fatty liver, metabolic dyslipidaemia and their links to insulin resistance,” Current Opinion in Lipidology, vol. 21, no. 4, pp. 329–336, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Kersten, J. Seydoux, J. M. Peters, F. J. Gonzalez, B. Desvergne, and W. Wahli, “Peroxisome proliferator-activated receptor α mediates the adaptive response to fasting,” Journal of Clinical Investigation, vol. 103, no. 11, pp. 1489–1498, 1999. View at Scopus
  96. G. Masterton, J. Plevris, and P. Hayes, “Review article: omega-3 fatty acids—a promising novel therapy for non-alcoholic fatty liver disease,” Alimentary Pharmacology and Therapeutics, vol. 31, no. 7, pp. 679–692, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. N. Yahagi, H. Shimano, A. H. Hasty et al., “A crucial role of sterol regulatory element-binding protein-1 in the regulation of lipogenic gene expression by polyunsaturated fatty acids,” Journal of Biological Chemistry, vol. 274, no. 50, pp. 35840–35844, 1999. View at Publisher · View at Google Scholar · View at Scopus
  98. W. J. Malaisse, N. Bulur, Y. Zhang et al., “The metabolic syndrome of ω3-depleted rats. I. Liver data,” International Journal of Molecular Medicine, vol. 24, no. 1, pp. 111–123, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. L. A. Videla, R. Rodrigo, J. Araya, and J. Poniachik, “Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease,” Free Radical Biology and Medicine, vol. 37, no. 9, pp. 1499–1507, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  100. S. Narasimhan, K. Gokulakrishnan, R. Sampathkumar et al., “Oxidative stress is independently associated with non-alcoholic fatty liver disease (NAFLD) in subjects with and without type 2 diabetes,” Clinical Biochemistry, vol. 43, no. 10-11, pp. 815–821, 2010. View at Publisher · View at Google Scholar · View at Scopus
  101. N. Chalasani, M. A. Deeg, and D. W. Crabb, “Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with nonalcoholic steatohepatitis,” American Journal of Gastroenterology, vol. 99, no. 8, pp. 1497–1502, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  102. Z. Yesilova, H. Yaman, C. Oktenli et al., “Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic fatty liver disease,” American Journal of Gastroenterology, vol. 100, no. 4, pp. 850–855, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  103. S. Seki, T. Kitada, T. Yamada, H. Sakaguchi, K. Nakatani, and K. Wakasa, “In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases,” Journal of Hepatology, vol. 37, no. 1, pp. 56–62, 2002. View at Publisher · View at Google Scholar · View at Scopus
  104. A. E. Feldstein, N. W. Werneburg, A. Canbay et al., “Free fatty acids promote hepatic lipotoxicity by stimulating TNF-α expression via a lysosomal pathway,” Hepatology, vol. 40, no. 1, pp. 185–194, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  105. J. P. Allard, E. Aghdassi, S. Mohammed et al., “Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): a cross-sectional study,” Journal of Hepatology, vol. 48, no. 2, pp. 300–307, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  106. A. Sevanian and P. Hochstein, “Mechanisms and consequences of lipid peroxidation in biological systems,” Annual Review of Nutrition, vol. 5, pp. 365–390, 1985. View at Scopus
  107. Y. B. Lombardo and A. G. Chicco, “Effects of dietary polyunsaturated n-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans. A review,” Journal of Nutritional Biochemistry, vol. 17, no. 1, pp. 1–13, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  108. R. Vuppalanchi, O. W. Cummings, R. Saxena et al., “Relationship among histologic, radiologic, and biochemical assessments of hepatic steatosis: a study of human liver samples,” Journal of Clinical Gastroenterology, vol. 41, no. 2, pp. 206–210, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  109. F. Montecucco and F. Mach, “Atherosclerosis is an Inflammatory Disease,” Seminars in Immunopathology, Springer, New York, NY, USA, 2009.
  110. U. N. Das, “A defect in the activity of δ6 and δ5 desaturases may be a factor in the initiation and progression of atherosclerosis,” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 76, no. 5, pp. 251–268, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  111. H. O. Bang and J. Dyerberg, “Lipid metabolism and ischemic heart disease in Greenland Eskimos,” Acta Medica Scandinavica, vol. 200, pp. 69–73, 1976.
  112. A. Menotti, D. Kromhout, H. Blackburn, F. Fidanza, R. Buzina, and A. Nissinen, “Food intake patterns and 25-year mortality from coronary heart disease: cross-cultural correlations in the Seven Countries Study,” European Journal of Epidemiology, vol. 15, no. 6, pp. 507–515, 1999. View at Publisher · View at Google Scholar · View at Scopus
  113. B. J. Holub, “Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care,” Canadian Medical Association Journal, vol. 166, no. 5, pp. 608–615, 2002.
  114. R. N. Lemaitre, I. B. King, D. Mozaffarian, L. H. Kuller, R. P. Tracy, and D. S. Siscovick, “n-3 polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study,” American Journal of Clinical Nutrition, vol. 77, no. 2, pp. 319–325, 2003. View at Scopus
  115. K. He, Y. Song, M. L. Daviglus et al., “Accumulated evidence on fish consumption and coronary heart disease mortality—a meta-analysis of cohort studies,” Circulation, vol. 109, no. 22, pp. 2705–2711, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  116. D. Mozaffarian, A. Geelen, I. A. Brouwer, J. M. Geleijnse, P. L. Zock, and M. B. Katan, “Effect of fish oil on heart rate in humans—a meta-analysis of randomized controlled trials,” Circulation, vol. 112, no. 13, pp. 1945–1952, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  117. M. M. Sellers and J. N. Stallone, “Sympathy for the devil: the role of thromboxane in the regulation of vascular tone and blood pressure,” American Journal of Physiology: Heart and Circulatory Physiology, vol. 294, no. 5, pp. H1978–H1986, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  118. T. Kobayashi, Y. Tahara, M. Matsumoto et al., “Roles of thromboxane A~2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice,” Journal of Clinical Investigation, vol. 114, no. 6, pp. 784–794, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. W. S. Harris, D. Mozaffarian, E. Rimm et al., “Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association nutrition subcommittee of the council on nutrition, physical activity, and metabolism; council on cardiovascular nursing; and council on epidemiology and prevention,” Circulation, vol. 119, no. 6, pp. 902–907, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  120. F. Maingrette and G. Renier, “Linoleic acid increases lectin-like oxidized LDL receptor-1 (LOX-1) expression in human aortic endothelial cells,” Diabetes, vol. 54, no. 5, pp. 1506–1513, 2005. View at Publisher · View at Google Scholar · View at Scopus
  121. A. P. Simopoulos, “The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases,” Experimental Biology and Medicine, vol. 233, no. 6, pp. 674–688, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  122. J. Prescott, D. Owens, P. Collins, A. Johnson, and G. H. Tomkin, “The fatty acid distribution in low density lipoprotein in diabetes,” Biochimica et Biophysica Acta: Molecular and Cell Biology of Lipids, vol. 1439, no. 1, pp. 110–116, 1999. View at Publisher · View at Google Scholar · View at Scopus
  123. J. Regnstrom, J. Nilsson, P. Tornvall, C. Landou, and A. Hamsten, “Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man,” Lancet, vol. 339, no. 8803, pp. 1183–1186, 1992. View at Publisher · View at Google Scholar · View at Scopus
  124. Y. A. Liou, D. J. King, D. Zibrik, and S. M. Innis, “Decreasing linoleic acid with constant α-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men,” Journal of Nutrition, vol. 137, no. 4, pp. 945–952, 2007. View at Scopus
  125. A. J. Lucendo and L. C. de Rezende, “Importance of nutrition in inflammatory bowel disease,” World Journal of Gastroenterology, vol. 15, no. 17, pp. 2081–2088, 2009. View at Publisher · View at Google Scholar · View at Scopus
  126. K. D. Cashman and F. Shanahan, “Is nutrition an aetiological factor for inflammatory bowel disease?” European Journal of Gastroenterology and Hepatology, vol. 15, no. 6, pp. 607–613, 2003. View at Publisher · View at Google Scholar · View at Scopus
  127. N. Kromann and A. Green, “Epidemiological studies in the Upernavik district, Greenland,” Acta Medica Scandinavica, vol. 208, no. 5, pp. 401–406, 1980. View at Scopus
  128. H. Bang, J. Dyerberg, and H. M. Sinclair, “The composition of the Eskimo food in north Western Greenland,” American Journal of Clinical Nutrition, vol. 33, no. 12, pp. 2657–2661, 1980. View at Scopus
  129. T. Shimizu, T. Fujii, R. Suzuki et al., “Effects of highly purified eicosapentaenoic acid on erythrocyte fatty acid composition and leukocyte and colonic mucosa leukotriene B4 production in children with ulcerative colitis,” Journal of Pediatric Gastroenterology and Nutrition, vol. 37, no. 5, pp. 581–585, 2003. View at Publisher · View at Google Scholar · View at Scopus
  130. A. B. Hawthorne, T. K. Daneshmend, C. J. Hawkey a et al., “Treatment of ulcerative colitis with fish oil supplementation—a prospective 12 month randomised controlled trial,” Gut, vol. 33, no. 7, pp. 922–928, 1992. View at Scopus
  131. R. S. Chapkin, L. A. Davidson, L. Ly, B. R. Weeks, J. R. Lupton, and D. N. McMurray, “Immunomodulatory effects of (n-3) fatty acids: putative link to inflammation and colon cancer,” Journal of Nutrition, vol. 137, no. 1, pp. 200s–204s, 2007. View at Scopus
  132. N. Sakamoto, S. Kono, K. Wakai et al., “Dietary risk factors for inflammatory bowel disease: a multicenter case-control study in Japan,” Inflammatory Bowel Diseases, vol. 11, no. 2, pp. 154–163, 2005. View at Publisher · View at Google Scholar · View at Scopus
  133. R. Shoda, K. Matsueda, S. Yamato, and N. Umeda, “Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan,” American Journal of Clinical Nutrition, vol. 63, no. 5, pp. 741–745, 1996. View at Scopus
  134. P. Sharon and W. F. Stenson, “enhanced synthesis of leukotriene-B4 by colonic mucosa in inflammatory bowel-disease,” Gastroenterology, vol. 86, no. 3, pp. 453–460, 1984. View at Scopus
  135. A. Belluzzi, C. Brignola, M. Campieri, A. Pera, S. Boschi, and M. Miglioli, “Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease,” New England Journal of Medicine, vol. 334, no. 24, pp. 1557–1560, 1996. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  136. L. Ferrucci, A. Cherubini, S. Bandinelli et al., “Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 2, pp. 439–446, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  137. J. W. C. Sijben and P. C. Calder, “Differential immunomodulation with long-chain n-3 PUFA in health and chronic disease,” Proceedings of the Nutrition Society, vol. 66, no. 2, pp. 237–259, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  138. P. C. Calder, “PUFA, inflammatory processes and rheumatoid arthritis,” Proceedings of the Nutrition Society, vol. 67, no. 4, pp. 409–418, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  139. T. Honda, E. Segi-Nishida, Y. Miyachi, and S. Narumiya, “Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis,” Journal of Experimental Medicine, vol. 203, no. 2, pp. 325–335, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  140. C. L. Curtis, C. E. Hughes, C. R. Flannery, C. B. Little, J. L. Harwood, and B. Caterson, “n-3 Fatty acids specifically modulate catabolic factors involved in articular cartilage degradation,” Journal of Biological Chemistry, vol. 275, no. 2, pp. 721–724, 2000. View at Publisher · View at Google Scholar · View at Scopus
  141. O. Adam, C. Beringer, T. Kless et al., “Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis,” Rheumatology International, vol. 23, no. 1, pp. 27–36, 2003. View at Scopus
  142. I. Björkhem, A. Cedazo-Minguez, V. Leoni, and S. Meaney, “Oxysterols and neurodegenerative diseases,” Molecular Aspects of Medicine, vol. 30, no. 3, pp. 171–179, 2009. View at Publisher · View at Google Scholar · View at Scopus
  143. J. Whelan, “(n-6) and (n-3) polyunsaturated fatty acids and the aging brain: food for thought,” Journal of Nutrition, vol. 138, no. 12, pp. 2521–2522, 2008. View at Publisher · View at Google Scholar · View at Scopus
  144. S. M. Rothman and M. P. Mattson, “Adverse stress, hippocampal networks, and Alzheimer's disease,” NeuroMolecular Medicine, vol. 12, no. 1, pp. 56–70, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  145. H. P. Lee, X. Zhu, G. Casadesus et al., “Antioxidant approaches for the treatment of Alzheimers disease,” Expert Review of Neurotherapeutics, vol. 10, no. 7, pp. 1201–1208, 2010. View at Publisher · View at Google Scholar · View at Scopus
  146. A. A. Farooqui, L. A. Horrocks, and T. Farooqui, “Modulation of inflammation in brain: a matter of fat,” Journal of Neurochemistry, vol. 101, no. 3, pp. 577–599, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  147. D. Tassoni, G. Kaur, R. S. Weisinger, and A. J. Sinclair, “The role of eicosanoids in the brain,” Asia Pacific Journal of Clinical Nutrition, vol. 17, supplement 1, pp. 220–228, 2008. View at Scopus
  148. F. Calon, G. P. Lim, T. Morihara et al., “Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease,” European Journal of Neuroscience, vol. 22, no. 3, pp. 617–626, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  149. E. J. Schaefer, V. Bongard, A. S. Beiser et al., “Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study,” Archives of Neurology, vol. 63, no. 11, pp. 1545–1550, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  150. M. Hashimoto, S. Hossain, T. Shimada et al., “Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats,” Journal of Neurochemistry, vol. 81, no. 5, pp. 1084–1091, 2002. View at Publisher · View at Google Scholar · View at Scopus
  151. G. P. Lim, F. Calon, T. Morihara et al., “A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model,” Journal of Neuroscience, vol. 25, no. 12, pp. 3032–3040, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  152. A. Dangour, E. Allen, D. Elbourne, A. Fletcher, M. Richards, and R. Uauy, “Fish consumption and cognitive function among older people in the UK: baseline data from the OPAL study,” Journal of Nutrition, Health and Aging, vol. 13, no. 3, pp. 198–202, 2009.
  153. M. P. Freeman, J. R. Hibbeln, K. L. Wisner et al., “Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry,” Journal of Clinical Psychiatry, vol. 67, no. 12, pp. 1954–1967, 2006. View at Scopus
  154. E. Freemantle, M. Vandal, J. Tremblay-Mercier et al., “Omega-3 fatty acids, energy substrates, and brain function during aging,” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 75, no. 3, pp. 213–220, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  155. C. Samieri, C. Féart, L. Letenneur et al., “Low plasma eicosapentaenoic acid and depressive symptomatology are independent predictors of dementia risk,” American Journal of Clinical Nutrition, vol. 88, no. 3, pp. 714–721, 2008. View at Scopus
  156. T. Dinan, L. Siggins, P. Scully, S. O'Brien, P. Ross, and C. Stanton, “Investigating the inflammatory phenotype of major depression: focus on cytokines and polyunsaturated fatty acids,” Journal of Psychiatric Research, vol. 43, no. 4, pp. 471–476, 2009. View at Publisher · View at Google Scholar · View at PubMed