924
Views
4
CrossRef citations to date
0
Altmetric
Reviews

Interaction between iron and omega-3 fatty acids metabolisms: where is the cross-link?

ORCID Icon, &

References

  • Agrawal, S., J. Fox, B. Thyagarajan, and J. H. Fox. 2018. Brain mitochondrial iron accumulates in Huntington's disease, mediates mitochondrial dysfunction, and can be removed pharmacologically. Free Radical Biology & Medicine 120:317–29. doi: 10.1016/j.freeradbiomed.2018.04.002.
  • Andersen, R., A. Biltoft-Jensen, T. Christensen, E. W. Andersen, M. Ege, A. V. Thorsen, S. M. Dalskov, C. T. Damsgaard, A. Astrup, K. F. Michaelsen, et al. 2014. Dietary effects of introducing school meals based on the New Nordic Diet - a randomised controlled trial in Danish children. The OPUS School Meal Study. British Journal of Nutrition 111 (11):1967–76. doi: 10.1017/S0007114514000634.
  • Anderson, E. R., and Y. M. Shah. 2013. Iron homeostasis in the liver. Comprehensive Physiology 3 (1):315–30. doi: 10.1002/cphy.c120016.
  • Anthonymuthu, T. S., Y. Y. Tyurina, W. Y. Sun, K. Mikulska-Ruminska, I. H. Shrivastava, V. A. Tyurin, F. B. Cinemre, H. H. Dar, A. P. VanDemark, T. R. Holman, et al. 2020. Resolving the paradox of ferroptotic cell death: Ferrostatin-1 binds to 15LOX/PEBP1 complex, suppresses generation of peroxidized ETE-PE, and protects against ferroptosis. Redox Biology 38:101744. doi: 10.1016/j.redox.2020.101744.
  • Ashok, A., and N. Singh. 2018. Prion protein modulates glucose homeostasis by altering intracellular iron. Scientific reports 8 (1):6556. doi: 10.1038/s41598-018-24786-1.
  • Ayton, S., P. Lei, and A. I. Bush. 2013. Metallostasis in Alzheimer's disease. Free Radical Biology & Medicine 62:76–89. doi: 10.1016/j.freeradbiomed.2012.10.558.
  • Balvers, M. G., K. C. Verhoeckx, P. Plastina, H. M. Wortelboer, J. Meijerink, and R. F. Witkamp. 2010. Docosahexaenoic acid and eicosapentaenoic acid are converted by 3T3-L1 adipocytes to N-acyl ethanolamines with anti-inflammatory properties. Biochimica et Biophysica Acta 1801 (10):1107–14. doi: 10.1016/j.bbalip.2010.06.006.
  • Barrera, C., R. Valenzuela, M. A. Rincon, A. Espinosa, S. Lopez-Arana, D. Gonzalez-Manan, N. Romero, R. Vargas, and L. A. Videla. 2020. Iron-induced derangement in hepatic Delta-5 and Delta-6 desaturation capacity and fatty acid profile leading to steatosis: Impact on extrahepatic tissues and prevention by antioxidant-rich extra virgin olive oil. Prostaglandins Leukot Essent Fatty Acids 153:102058. doi: 10.1016/j.plefa.2020.102058.
  • Barros, K. V., P. O. Carvalho, A. P. Cassulino, I. Andrade, A. L. West, E. A. Miles, P. C. Calder, and V. L. Silveira. 2013. Fatty acids in plasma, white and red blood cells, and tissues after oral or intravenous administration of fish oil in rats. Clinical Nutrition (Edinburgh, Scotland) 32 (6):993–8. doi: 10.1016/j.clnu.2013.02.010.
  • Baumgartner, J., C. M. Smuts, L. Malan, M. Arnold, B. K. Yee, L. E. Bianco, M. V. Boekschoten, M. Muller, W. Langhans, R. F. Hurrell, et al. 2012a. Combined deficiency of iron and (n-3) fatty acids in male rats disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone. The Journal of Nutrition 142 (8):1463–71. doi: 10.3945/jn.111.156281.
  • Baumgartner, J., C. M. Smuts, L. Malan, M. Arnold, B. K. Yee, L. E. Bianco, M. V. Boekschoten, M. Muller, W. Langhans, R. F. Hurrell, et al. 2012b. In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency. The Journal of Nutrition 142 (8):1472–8. doi: 10.3945/jn.111.156299.
  • Baumgartner, J., C. M. Smuts, L. Malan, J. Kvalsvig, M. E. van Stuijvenberg, R. F. Hurrell, and M. B. Zimmermann. 2012. Effects of iron and n-3 fatty acid supplementation, alone and in combination, on cognition in school children: A randomized, double-blind, placebo-controlled intervention in South Africa. The American Journal of Clinical Nutrition 96 (6):1327–38. doi: 10.3945/ajcn.112.041004.
  • Baumgartner, J., C. M. Smuts, and M. B. Zimmermann. 2014. Providing male rats deficient in iron and n-3 fatty acids with iron and alpha-linolenic acid alone affects brain serotonin and cognition differently from combined provision. Lipids in Health and Disease 13:97. doi: 10.1186/1476-511X-13-97.
  • Beard, J. 2003. Iron deficiency alters brain development and functioning. The Journal of nutrition 133 (5 Suppl 1):1468S–72S. doi: 10.1093/jn/133.5.1468S.
  • Beard, J. L. 2001. Iron biology in immune function, muscle metabolism and neuronal functioning. The Journal of Nutrition 131 (2S-2):568S–79S. doi: 10.1093/jn/131.2.568S.
  • Beard, J. L., and J. R. Connor. 2003. Iron status and neural functioning. Annual Review of Nutrition 23:41–58. doi: 10.1146/annurev.nutr.23.020102.075739.
  • Belaidi, A. A., and A. I. Bush. 2016. Iron neurochemistry in Alzheimer's disease and Parkinson's disease: Targets for therapeutics. Journal of Neurochemistry 139 Suppl 1:179–97. doi: 10.1111/jnc.13425.
  • Belot, A., O. Gourbeyre, A. Palin, A. Rubio, A. Largounez, C. Besson-Fournier, C. Latour, M. Lorgouilloux, I. Gallitz, A. Montagner, et al. 2020. Endoplasmic reticulum stress controls iron metabolism through TMPRSS6 repression and hepcidin mRNA stabilization by RNA-binding protein HuR. Haematologica. doi: 10.3324/haematol.2019.237321..
  • Benito, P., W. House, and D. Miller. 1998. Comparison of oral and intraperitoneal iron supplementation in anaemic rats: A re-evaluation of the mucosal block theory of iron absorption. The British Journal of Nutrition 79 (6):533–40. doi: 10.1079/bjn19980092.
  • Bentsen, H. 2017. Dietary polyunsaturated fatty acids, brain function and mental health. Microbial Ecology in Health and Disease 28 (sup1):1281916.
  • Berard, A. M., M. F. Dumon, and M. Darmon. 2004. Dietary fish oil up-regulates cholesterol 7alpha-hydroxylase mRNA in mouse liver leading to an increase in bile acid and cholesterol excretion. FEBS Letters 559 (1–3):125–8. doi: 10.1016/S0014-5793(04)00049-3.
  • Berg, J. M., J. L. Tymoczko, and L. Stryer. 2002. Glycolysis is an energy-conversion pathway in many organisms. In Biochemistry. 5th ed. New York: WH Freeman. ISBN-10: 0-7167-3051-0.
  • Bothwell, T. H. 2000. Iron requirements in pregnancy and strategies to meet them. The American Journal of Clinical Nutrition 72 (1 Suppl):257S–64S. doi: 10.1093/ajcn/72.1.257S.
  • Bourre, J. M., M. Francois, A. Youyou, O. Dumont, M. Piciotti, G. Pascal, and G. Durand. 1989. The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. The Journal of Nutrition 119 (12):1880–92. doi: 10.1093/jn/119.12.1880.
  • Boutaud, O., and A. R. Brash. 1999. Purification and catalytic activities of the two domains of the allene oxide synthase-lipoxygenase fusion protein of the coral Plexaura homomalla. The Journal of Biological Chemistry 274 (47):33764–70. doi: 10.1074/jbc.274.47.33764.
  • Brand, A., E. Schonfeld, I. Isharel, and E. Yavin. 2008. Docosahexaenoic acid-dependent iron accumulation in oligodendroglia cells protects from hydrogen peroxide-induced damage. Journal of Neurochemistry 105 (4):1325–35. doi: 10.1111/j.1471-4159.2008.05234.x.
  • Brand, A., and E. Yavin. 2001. Early ethanolamine phospholipid translocation marks stress-induced apoptotic cell death in oligodendroglial cells. Journal of Neurochemistry 78 (6):1208–18. doi: 10.1046/j.1471-4159.2001.00496.x.
  • Brand, A., and E. Yavin. 2005. Translocation of ethanolamine phosphoglyceride is required for initiation of apoptotic death in OLN-93 oligodendroglial cells. Neurochemical Research 30 (10):1257–67. doi: 10.1007/s11064-005-8797-9.
  • Britton, L. J., V. N. Subramaniam, and D. H. Crawford. 2016. Iron and non-alcoholic fatty liver disease. World Journal of Gastroenterology 22 (36):8112–22. doi: 10.3748/wjg.v22.i36.8112.
  • Bu, X. L., Y. Xiang, and Y. Guo. 2019. The role of iron in amyotrophic lateral sclerosis. Advances in Experimental Medicine and Biology 1173:145–52. doi: 10.1007/978-981-13-9589-5_8.
  • Buist, P. H. 2004. Fatty acid desaturases: Selecting the dehydrogenation channel. Natural Product Reports 21 (2):249–62. doi: 10.1039/B302094K.
  • Burdge, G. C., A. E. Jones, and S. A. Wootton. 2002. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*. The British Journal of Nutrition 88 (4):355–63. doi: 10.1079/BJN2002662.
  • Calder, P. C. 2017. Omega-3 fatty acids and inflammatory processes: From molecules to man. Biochemical Society Transactions 45 (5):1105–15. doi: 10.1042/BST20160474.
  • Camaschella, C. 2017. New insights into iron deficiency and iron deficiency anemia. Blood Reviews 31 (4):225–33. doi: 10.1016/j.blre.2017.02.004.
  • Camaschella, C., and A. Nai. 2016. Ineffective erythropoiesis and regulation of iron status in iron loading anaemias. British Journal of Haematology 172 (4):512–23. doi: 10.1111/bjh.13820.
  • Cardoso, B. R., D. J. Hare, A. I. Bush, and B. R. Roberts. 2017. Glutathione peroxidase 4: A new player in neurodegeneration? Molecular Psychiatry 22 (3):328–35. doi: 10.1038/mp.2016.196.
  • Casanas-Sanchez, V., J. A. Perez, N. Fabelo, A. V. Herrera-Herrera, C. Fernandez, R. Marin, M. C. Gonzalez-Montelongo, and M. Diaz. 2014. Addition of docosahexaenoic acid, but not arachidonic acid, activates glutathione and thioredoxin antioxidant systems in murine hippocampal HT22 cells: Potential implications in neuroprotection. Journal of Neurochemistry 131 (4):470–83. doi: 10.1111/jnc.12833.
  • Caughey, G. E., E. Mantzioris, R. A. Gibson, L. G. Cleland, and M. J. James. 1996. The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. The American Journal of Clinical Nutrition 63 (1):116–22. doi: 10.1093/ajcn/63.1.116.
  • Chen, C. T., Z. Liu, M. Ouellet, F. Calon, and R. P. Bazinet. 2009. Rapid beta-oxidation of eicosapentaenoic acid in mouse brain: An in situ study. Prostaglandins, Leukotrienes, and Essential Fatty Acids 80 (2–3):157–63. doi: 10.1016/j.plefa.2009.01.005.
  • Chen, L., S. Xiong, H. She, S. W. Lin, J. Wang, and H. Tsukamoto. 2007. Iron causes interactions of TAK1, p21ras, and phosphatidylinositol 3-kinase in caveolae to activate IkappaB kinase in hepatic macrophages. The Journal of Biological Chemistry 282 (8):5582–8. doi: 10.1074/jbc.M609273200.
  • Chen, W., X. Wang, L. I. Huang, and B. O. Liu. 2016. Hepcidin in non-alcoholic fatty liver disease regulated by the TLR4/NF-kappaB signaling pathway. Experimental and Therapeutic Medicine 11 (1):73–6. doi: 10.3892/etm.2015.2873.
  • Connor, J. R., K. L. Boeshore, S. A. Benkovic, and S. L. Menzies. 1994. Isoforms of ferritin have a specific cellular distribution in the brain. Journal of Neuroscience Research 37 (4):461–5. doi: 10.1002/jnr.490370405.
  • Connor, J. R., B. S. Snyder, J. L. Beard, R. E. Fine, and E. J. Mufson. 1992. Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease. Journal of Neuroscience Research 31 (2):327–35. doi: 10.1002/jnr.490310214.
  • Cooper, K. F., M. S. Scarnati, E. Krasley, M. J. Mallory, C. Jin, M. J. Law, and R. Strich. 2012. Oxidative-stress-induced nuclear to cytoplasmic relocalization is required for Not4-dependent cyclin C destruction. Journal of Cell Science 125 (Pt 4):1015–26. doi: 10.1242/jcs.096479.
  • Cotticelli, M. G., A. M. Crabbe, R. B. Wilson, and M. S. Shchepinov. 2013. Insights into the role of oxidative stress in the pathology of Friedreich ataxia using peroxidation resistant polyunsaturated fatty acids. Redox Biology 1:398–404. doi: 10.1016/j.redox.2013.06.004.
  • Crichton, R. R., and R. J. Ward. 1992. Iron metabolism-new perspectives in view. Biochemistry 31 (46):11255–64. doi: 10.1021/bi00161a001.
  • Czyż, K., R. Bodkowski, G. Herbinger, and T. Librowski. 2016. Omega-3 fatty acids and their role in central nervous system-A review. Current Medicinal Chemistry 23 (8):816–31. doi: 10.2174/0929867323666160122114439.
  • Darwesh, A. M., D. K. Sosnowski, T. Y. Lee, H. Keshavarz-Bahaghighat, and J. M. Seubert. 2019. Insights into the cardioprotective properties of n-3 PUFAs against ischemic heart disease via modulation of the innate immune system. Chemico-Biological Interactions 308:20–44. doi: 10.1016/j.cbi.2019.04.037.
  • de Assis, A. M., A. Rech, A. Longoni, L. N. Rotta, C. C. Denardin, M. A. Pasquali, D. O. Souza, M. L. Perry, and J. C. Moreira. 2012. Ω3-Polyunsaturated fatty acids prevent lipoperoxidation, modulate antioxidant enzymes, and reduce lipid content but do not alter glycogen metabolism in the livers of diabetic rats fed on a high fat thermolyzed diet. Molecular and Cellular Biochemistry 361 (1–2):151–60. doi: 10.1007/s11010-011-1099-4.
  • De Felice, F. G., M. V. Lourenco, and S. T. Ferreira. 2014. How does brain insulin resistance develop in Alzheimer's disease? Alzheimer's & Dementia: The Journal of the Alzheimer's Association 10 (1 Suppl):S26–S32. doi: 10.1016/j.jalz.2013.12.004.
  • De Gobbi, M., and A. Roetto. 1993. TFR2-related hereditary hemochromatosis. In GeneReviews((R)), eds. M. P. Adam, H. H. Ardinger, R. A. Pagon, S. E. Wallace, L. J. H. Bean, K. Stephens and A. Amemiya. Seattle (WA): University of Washington.ISSN: 2372–0697.
  • Demar, J. C., Jr., K. Ma, L. Chang, J. M. Bell, and S. I. Rapoport. 2005. alpha-Linolenic acid does not contribute appreciably to docosahexaenoic acid within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic acid. Journal of Neurochemistry 94 (4):1063–76. doi: 10.1111/j.1471-4159.2005.03258.x.
  • Devos, D., Z. I. Cabantchik, C. Moreau, V. Danel, L. Mahoney-Sanchez, H. Bouchaoui, F. Gouel, A. S. Rolland, J. A. Duce, and J. C. Devedjian, FAIRPARK-II and FAIRALS-II studygroups. 2020. Conservative iron chelation for neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis. Journal of Neural Transmission (Vienna, Austria : 1996) 127 (2):189–203. doi: 10.1007/s00702-019-02138-1.
  • Diaz-Castro, J., J. Moreno-Fernandez, S. Hijano, N. Kajarabille, M. Pulido-Moran, G. O. Latunde-Dada, J. A. Hurtado, M. Pena, L. Pena-Quintana, F. Lara-Villoslada, et al. 2015. DHA supplementation: A nutritional strategy to improve prenatal Fe homeostasis and prevent birth outcomes related with Fe-deficiency. Journal of Functional Foods 19:385–93. doi: 10.1016/j.jff.2015.09.051.
  • Dixon, S. J., K. M. Lemberg, M. R. Lamprecht, R. Skouta, E. M. Zaitsev, C. E. Gleason, D. N. Patel, A. J. Bauer, A. M. Cantley, W. S. Yang, et al. 2012. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell 149 (5):1060–72. doi: 10.1016/j.cell.2012.03.042.
  • Donovan, A., C. A. Lima, J. L. Pinkus, G. S. Pinkus, L. I. Zon, S. Robine, and N. C. Andrews. 2005. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metabolism 1 (3):191–200. doi: 10.1016/j.cmet.2005.01.003.
  • Drakesmith, H., E. Nemeth, and T. Ganz. 2015. Ironing out ferroportin. Cell Metabolism 22 (5):777–87. doi: 10.1016/j.cmet.2015.09.006.
  • Drayer, B. P. 1988. Imaging of the aging brain. Part II. Pathologic conditions. Radiology 166 (3):797–806. doi: 10.1148/radiology.166.3.3277248.
  • Dyall, S. C. 2015. Long-chain omega-3 fatty acids and the brain: A review of the independent and shared effects of EPA, DPA and DHA. Frontiers in Aging Neuroscience 7:52. doi: 10.3389/fnagi.2015.00052.
  • Edidin, M. 2003. The state of lipid rafts: From model membranes to cells. Annual Review of Biophysics and Biomolecular Structure 32 (1):257–83. doi: 10.1146/annurev.biophys.32.110601.142439.
  • Ekiz, C., L. Agaoglu, Z. Karakas, N. Gurel, and I. Yalcin. 2005. The effect of iron deficiency anemia on the function of the immune system. The Hematology Journal 5 (7):579–83. doi: 10.1038/sj.thj.6200574.
  • Falkingham, M., A. Abdelhamid, P. Curtis, S. Fairweather-Tait, L. Dye, and L. Hooper. 2010. The effects of oral iron supplementation on cognition in older children and adults: A systematic review and meta-analysis. Nutrition Journal 9 (4):4 doi: 10.1186/1475-2891-9-4.
  • Feder, J. N., A. Gnirke, W. Thomas, Z. Tsuchihashi, D. A. Ruddy, A. Basava, F. Dormishian, R. Domingo, Jr., M. C. Ellis, A. Fullan, et al. 1996. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics 13 (4):399–408. doi: 10.1038/ng0896-399.
  • Feng, D., D. Y. Youn, X. Zhao, Y. Gao, W. J. Quinn, 3rd, A. M. Xiaoli, Y. Sun, M. J. Birnbaum, J. E. Pessin, and F. Yang. 2015. mTORC1 down-regulates cyclin-dependent kinase 8 (CDK8) and cyclin C (CycC). PLoS One 10 (6):e0126240. doi: 10.1371/journal.pone.0126240.
  • Freemantle, E., M. Vandal, J. Tremblay-Mercier, S. Tremblay, J. C. Blachere, M. E. Begin, J. T. Brenna, A. Windust, and S. C. Cunnane. 2006. Omega-3 fatty acids, energy substrates, and brain function during aging. Prostaglandins Leukotrienes, and Essential Fatty Acids 75 (3):213–20. doi: 10.1016/j.plefa.2006.05.011.
  • Fujita, N., H. Miyachi, H. Tanaka, M. Takeo, N. Nakagawa, Y. Kobayashi, M. Iwasa, S. Watanabe, and Y. Takei. 2009. Iron overload is associated with hepatic oxidative damage to DNA in nonalcoholic steatohepatitis. Cancer Epidemiology Biomarkers & Prevention 18 (2):424–32. doi: 10.1158/1055-9965.EPI-08-0725.
  • Gambling, L., Z. Charania, L. Hannah, C. Antipatis, R. G. Lea, and H. J. McArdle. 2002. Effect of iron deficiency on placental cytokine expression and fetal growth in the pregnant rat. Biology of Reproduction 66 (2):516–23. doi: 10.1095/biolreprod66.2.516.
  • Gambling, L., S. Dunford, D. I. Wallace, G. Zuur, N. Solanky, S. K. Srai, and H. J. McArdle. 2003. Iron deficiency during pregnancy affects postnatal blood pressure in the rat. The Journal of Physiology 552 (Pt 2):603–10. doi: 10.1113/jphysiol.2003.051383.
  • Gao, L., J. Wang, K. R. Sekhar, H. Yin, N. F. Yared, S. N. Schneider, S. Sasi, T. P. Dalton, M. E. Anderson, J. Y. Chan, et al. 2007. Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. The Journal of Biological Chemistry 282 (4):2529–37. doi: 10.1074/jbc.M607622200.
  • Gholamhosseinian, A., R. Abbasalipourkabir, N. Ziamajidi, M. Sayadi, and K. Sayadi. 2020. The anti-inflammatory effect of omega-3 polyunsaturated fatty acids dramatically decreases by iron in the hippocampus of diabetic rats. Life Sciences 245:117393. doi: 10.1016/j.lfs.2020.117393.
  • Giordano, E., and F. Visioli. 2014. Long-chain omega 3 fatty acids: Molecular bases of potential antioxidant actions. Prostaglandins, Leukotrienes, and Essential Fatty Acids 90 (1):1–4. doi: 10.1016/j.plefa.2013.11.002.
  • Gorjao, R., A. K. Azevedo-Martins, H. G. Rodrigues, F. Abdulkader, M. Arcisio-Miranda, J. Procopio, and R. Curi. 2009. Comparative effects of DHA and EPA on cell function. Pharmacology & Therapeutics 122 (1):56–64. doi: 10.1016/j.pharmthera.2009.01.004.
  • Graham, R. M., A. C. Chua, K. W. Carter, R. D. Delima, D. Johnstone, C. E. Herbison, M. J. Firth, R. O'Leary, E. A. Milward, J. K. Olynyk, et al. 2010. Hepatic iron loading in mice increases cholesterol biosynthesis. Hepatology 52 (2):462–71. doi: 10.1002/hep.23712.
  • Gu, Y., R. S. Vorburger, Y. Gazes, C. G. Habeck, Y. Stern, J. A. Luchsinger, J. J. Manly, N. Schupf, R. Mayeux, and A. M. Brickman. 2016. White matter integrity as a mediator in the relationship between dietary nutrients and cognition in the elderly. Annals of Neurology 79 (6):1014–25. doi: 10.1002/ana.24674.
  • Gulec, S., G. J. Anderson, and J. F. Collins. 2014. Mechanistic and regulatory aspects of intestinal iron absorption. American Journal of Physiology. Gastrointestinal and Liver Physiology 307 (4):G397–409. doi: 10.1152/ajpgi.00348.2013.
  • Gunshin, H., B. Mackenzie, U. V. Berger, Y. Gunshin, M. F. Romero, W. F. Boron, S. Nussberger, J. L. Gollan, and M. A. Hediger. 1997. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388 (6641):482–8. doi: 10.1038/41343.
  • Haacke, E. M., N. Y. Cheng, M. J. House, Q. Liu, J. Neelavalli, R. J. Ogg, A. Khan, M. Ayaz, W. Kirsch, and A. Obenaus. 2005. Imaging iron stores in the brain using magnetic resonance imaging. Magnetic Resonance Imaging 23 (1):1–25. doi: 10.1016/j.mri.2004.10.001.
  • Hagopian, K., K. L. Weber, D. T. Hwee, A. L. Van Eenennaam, G. Lopez-Lluch, J. M. Villalba, I. Buron, P. Navas, J. B. German, S. M. Watkins, et al. 2010. Complex I-associated hydrogen peroxide production is decreased and electron transport chain enzyme activities are altered in n-3 enriched fat-1 mice. PLoS One 5 (9):e12696. doi: 10.1371/journal.pone.0012696.
  • Han, J., J. R. Day, J. R. Connor, and J. L. Beard. 2003. Gene expression of transferrin and transferrin receptor in brains of control vs. iron-deficient rats. Nutritional Neuroscience 6 (1):1–10.
  • Harahap, H.,. A. B. Jahari, M. A. Husaini, C. Saco-Pollitt, and E. Pollitt. 2000. Effects of an energy and micronutrient supplement on iron deficiency anemia, physical activity and motor and mental development in undernourished children in Indonesia. European Journal of Clinical Nutrition 54 (S2):S114–S9. doi: 10.1038/sj.ejcn.1601011.
  • Harris, S. S. 2002. The effect of calcium consumption on iron absorption and iron status. Nutrition in Clinical Care: An Official Publication of Tufts University 5 (5):231–5. doi: 10.1046/j.1523-5408.2002.05505.x.
  • Herguner, S., F. M. Kelesoglu, C. Tanidir, and M. Copur. 2012. Ferritin and iron levels in children with autistic disorder. European Journal of Pediatrics 171 (1):143–6. doi: 10.1007/s00431-011-1506-6.
  • Honda, H., N. Hosaka, T. Ganz, and T. Shibata. 2019. Iron metabolism in chronic kidney disease patients. Contributions to Nephrology 198:103–11. doi: 10.1159/000496369.
  • Hou, W., Y. Xie, X. Song, X. Sun, M. T. Lotze, H. J. Zeh, 3rd, R. Kang, and D. Tang. 2016. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12 (8):1425–8. doi: 10.1080/15548627.2016.1187366.
  • Hsu, H. C., C. Y. Chen, and M. F. Chen. 2014. N-3 polyunsaturated fatty acids decrease levels of doxorubicin-induced reactive oxygen species in cardiomyocytes - involvement of uncoupling protein UCP2. Journal of Biomedical Science 21 (101):101. doi: 10.1186/s12929-014-0101-3.
  • Hulbert, A. J., N. Turner, L. H. Storlien, and P. L. Else. 2005. Dietary fats and membrane function: Implications for metabolism and disease. Biological Reviews 80 (1):155–69. doi: 10.1017/s1464793104006578.
  • Jaeggi, T., G. A. Kortman, D. Moretti, C. Chassard, P. Holding, A. Dostal, J. Boekhorst, H. M. Timmerman, D. W. Swinkels, H. Tjalsma, et al. 2015. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut 64 (5):731–42. doi: 10.1136/gutjnl-2014-307720.
  • Jiang, B., G. Liu, J. Zheng, M. Chen, Z. Maimaitiming, M. Chen, S. Liu, R. Jiang, B. K. Fuqua, J. L. Dunaief, et al. 2016. Hephaestin and ceruloplasmin facilitate iron metabolism in the mouse kidney. Scientific Reports 6:39470. doi: 10.1038/srep39470.
  • Jiang, R., C. Hua, Y. Wan, B. Jiang, H. Hu, J. Zheng, B. K. Fuqua, J. L. Dunaief, G. J. Anderson, S. David, et al. 2015. Hephaestin and ceruloplasmin play distinct but interrelated roles in iron homeostasis in mouse brain. The Journal of Nutrition 145 (5):1003–9. doi: 10.3945/jn.114.207316.
  • Jump, D. B., K. A. Lytle, C. M. Depner, and S. Tripathy. 2018. Omega-3 polyunsaturated fatty acids as a treatment strategy for nonalcoholic fatty liver disease. Pharmacology & Therapeutics 181:108–25. doi: 10.1016/j.pharmthera.2017.07.007.
  • Kagan, V. E., G. Mao, F. Qu, J. P. Angeli, S. Doll, C. S. Croix, H. H. Dar, B. Liu, V. A. Tyurin, V. B. Ritov, et al. 2017. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nature Chemical Biology 13 (1):81–90. doi: 10.1038/nchembio.2238.
  • Kasbi Chadli, F., H. Nazih, M. Krempf, P. Nguyen, and K. Ouguerram. 2013. Omega 3 fatty acids promote macrophage reverse cholesterol transport in hamster fed high fat diet. PLoS One 8 (4):e61109. doi: 10.1371/journal.pone.0061109.
  • Keep, R. F., and H. C. Jones. 1990. Cortical microvessels during brain development: A morphometric study in the rat. Microvascular Research 40 (3):412–26. doi: 10.1016/0026-2862(90)90036-Q.
  • Kennedy, D. O., P. A. Jackson, J. M. Elliott, A. B. Scholey, B. C. Robertson, J. Greer, B. Tiplady, T. Buchanan, and C. F. Haskell. 2009. Cognitive and mood effects of 8 weeks' supplementation with 400 mg or 1000 mg of the omega-3 essential fatty acid docosahexaenoic acid (DHA) in healthy children aged 10-12 years. Nutritional Neuroscience 12 (2):48–56. doi: 10.1179/147683009X388887.
  • Kim, A., and E. Nemeth. 2015. New insights into iron regulation and erythropoiesis. Current Opinion in Hematology 22 (3):199–205. doi: 10.1097/MOH.0000000000000132.
  • Kim, J., and M. Wessling-Resnick. 2014. Iron and mechanisms of emotional behavior. The Journal of Nutritional Biochemistry 25 (11):1101–7. doi: 10.1016/j.jnutbio.2014.07.003.
  • Klei, T. R., S. M. Meinderts, T. K. van den Berg, and R. van Bruggen. 2017. From the cradle to the grave: The role of macrophages in erythropoiesis and erythrophagocytosis. Frontiers in Immunology 8:73. doi: 10.3389/fimmu.2017.00073.
  • Knutson, M. D. 2019. Non-transferrin-bound iron transporters. Free Radical Biology & Medicine 133:101–11. doi: 10.1016/j.freeradbiomed.2018.10.413.
  • Kovtunovych, G., M. C. Ghosh, W. Ollivierre, R. P. Weitzel, M. A. Eckhaus, J. F. Tisdale, A. Yachie, and T. A. Rouault. 2014. Wild-type macrophages reverse disease in heme oxygenase 1-deficient mice. Blood 124 (9):1522–30. doi: 10.1182/blood-2014-02-554162.
  • Kurian, M. A., A. McNeill, J. P. Lin, and E. R. Maher. 2011. Childhood disorders of neurodegeneration with brain iron accumulation (NBIA). Developmental Medicine and Child Neurology 53 (5):394–404. doi: 10.1111/j.1469-8749.2011.03955.x.
  • Lands, B. 2012. Consequences of essential fatty acids. Nutrients 4 (9):1338–57. doi: 10.3390/nu4091338.
  • Lane, D. J., S. R. Robinson, H. Czerwinska, G. M. Bishop, and A. Lawen. 2010. Two routes of iron accumulation in astrocytes: Ascorbate-dependent ferrous iron uptake via the divalent metal transporter (DMT1) plus an independent route for ferric iron. The Biochemical Journal 432 (1):123–32. doi: 10.1042/BJ20101317.
  • Latunde-Dada, G. O. 2017. Ferroptosis: Role of lipid peroxidation, iron and ferritinophagy. Biochimica et Biophysica Acta. General Subjects 1861 (8):1893–900. doi: 10.1016/j.bbagen.2017.05.019.
  • Laye, S., A. Nadjar, C. Joffre, and R. P. Bazinet. 2018. Anti-inflammatory effects of omega-3 fatty acids in the brain: Physiological mechanisms and relevance to pharmacology. Pharmacological Reviews 70 (1):12–38. doi: 10.1124/pr.117.014092.
  • Le Blanc, S., M. D. Garrick, and M. Arredondo. 2012. Heme carrier protein 1 transports heme and is involved in heme-Fe metabolism. American Journal of Physiology. Cell Physiology 302 (12):C1780–5. doi: 10.1152/ajpcell.00080.2012.
  • Lee, S., N. H. Kyung, S. Y. Ki, K. S. Eun, and A. W. Suk. 2019. Modulating hepcidin levels by vitamin D and omega-3 fatty acid in 5/6 nephrectomy rat model. Nephrology Dialysis Transplantation 34 (Supplement_1). doi: 10.1093/ndt/gfz103.SP350.
  • Levy, B. D. 2010. Resolvins and protectins: Natural pharmacophores for resolution biology. Prostaglandins, Leukotrienes, and Essential Fatty Acids 82 (4–6):327–32. doi: 10.1016/j.plefa.2010.02.003.
  • Lichtenstein, A. H., and P. J. Jones. 2001. Lipids: Absorption and transport. Present Knowledge in Nutrition 10:118–31.
  • Lin, Y. H., J. A. Brown, C. DiMartino, I. Dahms, N. Salem, Jr., and J. R. Hibbeln. 2016. Differences in long chain polyunsaturates composition and metabolism in male and female rats. Prostaglandins, Leukotrienes, and Essential Fatty Acids 113:19–27. doi: 10.1016/j.plefa.2016.08.008.
  • Lipinski, P., A. Stys, and R. R. Starzynski. 2013. Molecular insights into the regulation of iron metabolism during the prenatal and early postnatal periods. Cellular and Molecular Life Sciences 70 (1):23–38. doi: 10.1007/s00018-012-1018-1.
  • Lozoff, B., and M. K. Georgieff. 2006. Iron deficiency and brain development. Seminars in Pediatric Neurology 13 (3):158–65. doi: 10.1016/j.spen.2006.08.004.
  • Ma, Y., C. E. Smith, C. Q. Lai, M. R. Irvin, L. D. Parnell, Y. C. Lee, L. D. Pham, S. Aslibekyan, S. A. Claas, M. Y. Tsai, et al. 2016. The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter. Molecular Nutrition & Food Research 60 (2):410–9. doi: 10.1002/mnfr.201500436.
  • MacDonald, G. A., K. R. Bridle, P. J. Ward, N. I. Walker, K. Houglum, D. K. George, J. L. Smith, L. W. Powell, D. H. Crawford, and G. A. Ramm. 2001. Lipid peroxidation in hepatic steatosis in humans is associated with hepatic fibrosis and occurs predominately in acinar zone 3. Journal of Gastroenterology and Hepatology 16 (6):599–606. doi: 10.1046/j.1440-1746.2001.02445.x.
  • Magtanong, L., and S. J. Dixon. 2018. Ferroptosis and Brain Injury. Developmental Neuroscience 40 (5–6):382–95. doi: 10.1159/000496922.
  • Malan, L., J. Baumgartner, P. C. Calder, M. B. Zimmermann, and C. M. Smuts. 2015. n-3 Long-chain PUFAs reduce respiratory morbidity caused by iron supplementation in iron-deficient South African schoolchildren: A randomized, double-blind, placebo-controlled intervention. The American Journal of Clinical Nutrition 101 (3):668–79. doi: 10.3945/ajcn.113.081208.
  • Malan, L., J. Baumgartner, L. Zandberg, P. C. Calder, and C. M. Smuts. 2016. Iron and a mixture of DHA and EPA supplementation, alone and in combination, affect bioactive lipid signalling and morbidity of iron deficient South African school children in a two-by-two randomised controlled trial. Prostaglandins, Leukotrienes, and Essential Fatty Acids 105:15–25. doi: 10.1016/j.plefa.2015.12.005.
  • Masterton, G. S., J. N. Plevris, and P. C. Hayes. 2010. Review article: Omega-3 fatty acids - a promising novel therapy for non-alcoholic fatty liver disease. Alimentary Pharmacology & Therapeutics 31 (7):679–92. doi: 10.1111/j.1365-2036.2010.04230.x.
  • Maurice, J., and P. Manousou. 2018. Non-alcoholic fatty liver disease. Clinical Medicine (London, England) 18 (3):245–50. doi: 10.7861/clinmedicine.18-3-245.
  • Mazgaj, R., M. Szudzik, P. Lipiński, A. Jończy, E. Smuda, M. Kamyczek, B. Cieślak, D. Swinkels, M. Lenartowicz, and R. R. Starzyński. 2020. Effect of oral supplementation of healthy pregnant sows with sucrosomial ferric pyrophosphate on maternal iron status and hepatic iron stores in newborn piglets. Animals 10 (7):1113. doi:3390/ani10071113. doi: 10.3390/ani10071113.
  • McCarthy, R. C., and D. J. Kosman. 2015. Mechanisms and regulation of iron trafficking across the capillary endothelial cells of the blood-brain barrier. Frontiers in Molecular Neuroscience 8:31. doi: 10.3389/fnmol.2015.00031.
  • McCarthy, R. C., J. C. Sosa, A. M. Gardeck, A. S. Baez, C. H. Lee, and M. Wessling-Resnick. 2018. Inflammation-induced iron transport and metabolism by brain microglia. Journal of Biological Chemistry 293 (20):7853–63. doi: 10.1074/jbc.RA118.001949.
  • McKie, A. T., D. Barrow, G. O. Latunde-Dada, A. Rolfs, G. Sager, E. Mudaly, M. Mudaly, C. Richardson, D. Barlow, A. Bomford, et al. 2001. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science (New York, N.Y.) 291 (5509):1755–9. doi: 10.1126/science.1057206.
  • McNamara, R. K., I. J. Magrisso, R. Hofacer, R. Jandacek, T. Rider, P. Tso, and S. C. Benoit. 2012. Omega-3 fatty acid deficiency augments risperidone-induced hepatic steatosis in rats: Positive association with stearoyl-CoA desaturase. Pharmacological Research 66 (4):283–91. doi: 10.1016/j.phrs.2012.06.010.
  • Meijerink, J., P. Plastina, J. P. Vincken, M. Poland, M. Attya, M. Balvers, H. Gruppen, B. Gabriele, and R. F. Witkamp. 2011. The ethanolamide metabolite of DHA, docosahexaenoylethanolamine, shows immunomodulating effects in mouse peritoneal and RAW264.7 macrophages: Evidence for a new link between fish oil and inflammation. The British Journal of Nutrition 105 (12):1798–807. doi: 10.1017/S0007114510005635.
  • Meneghini, R. 1997. Iron homeostasis, oxidative stress, and DNA damage. Free Radical Biology & Medicine 23 (5):783–92. doi: 10.1016/S0891-5849(97)00016-6.
  • Meydani, S. N., S. Endres, M. M. Woods, B. R. Goldin, C. Soo, A. Morrill-Labrode, C. A. Dinarello, and S. L. Gorbach. 1991. Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: Comparison between young and older women. The Journal of Nutrition 121 (4):547–55. doi: 10.1093/jn/121.4.547.
  • Miller, L. E., G. R. McGinnis, B. Kliszczewicz, D. Slivka, W. Hailes, J. Cuddy, C. Dumke, B. Ruby, and J. C. Quindry. 2013. Blood oxidative-stress markers during a high-altitude trek. International Journal of Sport Nutrition and Exercise Metabolism 23 (1):65–72. doi: 10.1123/ijsnem.23.1.65.
  • Minamiyama, Y., S. Takemura, S. Kodai, H. Shinkawa, T. Tsukioka, H. Ichikawa, Y. Naito, T. Yoshikawa, and S. Okada. 2010. Iron restriction improves type 2 diabetes mellitus in Otsuka Long-Evans Tokushima fatty rats. American Journal of Physiology. Endocrinology and Metabolism 298 (6):E1140–9. doi: 10.1152/ajpendo.00620.2009.
  • Montosi, G., A. Donovan, A. Totaro, C. Garuti, E. Pignatti, S. Cassanelli, C. C. Trenor, P. Gasparini, N. C. Andrews, and A. Pietrangelo. 2001. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. The Journal of Clinical Investigation 108 (4):619–23. doi: 10.1172/JCI13468.
  • Moos, T., T. Rosengren Nielsen, T. Skjorringe, and E. H. Morgan. 2007. Iron trafficking inside the brain. Journal of Neurochemistry 103 (5):1730–40. doi: 10.1111/j.1471-4159.2007.04976.x.
  • Nakamura, M. T., and T. Y. Nara. 2004. Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annual Review of Nutrition 24:345–76. doi: 10.1146/annurev.nutr.24.121803.063211.
  • Nelson, J. E., H. Klintworth, and K. V. Kowdley. 2012. Iron metabolism in nonalcoholic fatty liver disease. Current Gastroenterology Reports 14 (1):8–16. doi: 10.1007/s11894-011-0234-4.
  • Nemeth, E., S. Rivera, V. Gabayan, C. Keller, S. Taudorf, B. K. Pedersen, and T. Ganz. 2004. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. The Journal of Clinical Investigation 113 (9):1271–6. doi: 10.1172/JCI20945.
  • Neuschwander-Tetri, B. A. 2017. Non-alcoholic fatty liver disease. BMC Medicine 15 (1):45. doi: 10.1186/s12916-017-0806-8.
  • Ohgami, R. S., D. R. Campagna, E. L. Greer, B. Antiochos, A. McDonald, J. Chen, J. J. Sharp, Y. Fujiwara, J. E. Barker, and M. D. Fleming. 2005. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nature Genetics 37 (11):1264–9. doi: 10.1038/ng1658.
  • Oski, F. A., A. S. Honig, B. Helu, and P. Howanitz. 1983. Effect of iron therapy on behavior performance in nonanemic, iron-deficient infants. Pediatrics 71 (6):877–80.
  • Ouellet, M., V. Emond, C. T. Chen, C. Julien, F. Bourasset, S. Oddo, F. LaFerla, R. P. Bazinet, and F. Calon. 2009. Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: An in situ cerebral perfusion study. Neurochemistry International. 55 (7):476–82. doi: 10.1016/j.neuint.2009.04.018.
  • Pala, E., M. Erguven, S. Guven, M. Erdogan, and T. Balta. 2010. Psychomotor development in children with iron deficiency and iron-deficiency anemia. Food and Nutrition Bulletin 31 (3):431–5. doi: 10.1177/156482651003100305.
  • Pantopoulos, K. 2018. Inherited disorders of iron overload. Frontiers in Nutrition 5:103. doi: 10.3389/fnut.2018.00103.
  • Pantopoulos, K., S. K. Porwal, A. Tartakoff, and L. Devireddy. 2012. Mechanisms of mammalian iron homeostasis. Biochemistry 51 (29):5705–24. doi: 10.1021/bi300752r.
  • Papanikolaou, G., M. E. Samuels, E. H. Ludwig, M. L. MacDonald, P. L. Franchini, M. P. Dube, L. Andres, J. MacFarlane, N. Sakellaropoulos, M. Politou, et al. 2004. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nature Genetics 36 (1):77–82. doi: 10.1038/ng1274.
  • Perez, M. A., L. Magtanong, S. J. Dixon, and J. L. Watts. 2020. Dietary Lipids Induce Ferroptosis in Caenorhabditiselegans and Human Cancer Cells. Developmental Cell 54 (4):447–54 e4. doi: 10.1016/j.devcel.2020.06.019.
  • Peterson, L. D., N. M. Jeffery, F. Thies, P. Sanderson, E. A. Newsholme, and P. C. Calder. 1998. Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity. Lipids 33 (2):171–80. doi: 10.1007/s11745-998-0193-y.
  • Pigeon, C., P. Legrand, P. Leroyer, M. Bouriel, B. Turlin, P. Brissot, and O. Loreal. 2001. Stearoyl coenzyme A desaturase 1 expression and activity are increased in the liver during iron overload. Biochimica et Biophysica Acta 1535 (3):275–84. doi: 10.1016/S0925-4439(01)00024-2.
  • Pivina, L., Y. Semenova, M. D. Doşa, M. Dauletyarova, and G. Bjørklund. 2019. Iron deficiency, cognitive functions, and neurobehavioral disorders in children. Journal of Molecular Neuroscience : MN 68 (1):1–10. doi: 10.1007/s12031-019-01276-1.
  • Pizzini, A., L. Lunger, E. Demetz, R. Hilbe, G. Weiss, C. Ebenbichler, and I. Tancevski. 2017. The Role of omega-3 fatty acids in reverse cholesterol transport: A review. Nutrients 9 (10):1099. doi: 10.3390/nu9101099.
  • Ponka, P., and C. N. Lok. 1999. The transferrin receptor: Role in health and disease. The International Journal of Biochemistry & Cell Biology 31 (10):1111–37. doi: 10.1016/S1357-2725(99)00070-9.
  • Ponugoti, B., D. H. Kim, Z. Xiao, Z. Smith, J. Miao, M. Zang, S. Y. Wu, C. M. Chiang, T. D. Veenstra, and J. K. Kemper. 2010. SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. The Journal of Biological Chemistry 285 (44):33959–70. doi: 10.1074/jbc.M110.122978.
  • Prasnicka, A., J. Cermanova, M. Hroch, E. Dolezelova, L. Rozkydalova, T. Smutny, A. Carazo, J. Chladek, M. Lenicek, P. Nachtigal, et al. 2017. Iron depletion induces hepatic secretion of biliary lipids and glutathione in rats. Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids 1862 (12):1469–80. doi: 10.1016/j.bbalip.2017.09.003.
  • Puri, P., R. A. Baillie, M. M. Wiest, F. Mirshahi, J. Choudhury, O. Cheung, C. Sargeant, M. J. Contos, and A. J. Sanyal. 2007. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 46 (4):1081–90. doi: 10.1002/hep.21763.
  • Qi, J., J. W. Kim, Z. Zhou, C. W. Lim, and B. Kim. 2020. Ferroptosis affects the progression of nonalcoholic steatohepatitis via the modulation of lipid peroxidation-mediated cell death in mice. The American Journal of Pathology 190 (1):68–81. doi: 10.1016/j.ajpath.2019.09.011.
  • Qiu, A., M. Jansen, A. Sakaris, S. H. Min, S. Chattopadhyay, E. Tsai, C. Sandoval, R. Zhao, M. H. Akabas, and I. D. Goldman. 2006. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 127 (5):917–28. doi: 10.1016/j.cell.2006.09.041.
  • Raha, A. A., R. A. Vaishnav, R. P. Friedland, A. Bomford, and R. Raha-Chowdhury. 2013. The systemic iron-regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer's disease. Acta Neuropathologica Communications 1:55. doi: 10.1186/2051-5960-1-55.
  • Rajagopal, A., A. U. Rao, J. Amigo, M. Tian, S. K. Upadhyay, C. Hall, S. Uhm, M. K. Mathew, M. D. Fleming, B. H. Paw, et al. 2008. Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins. Nature 453 (7198):1127–31. doi: 10.1038/nature06934.
  • Raji, C. A., K. I. Erickson, O. L. Lopez, L. H. Kuller, H. M. Gach, P. M. Thompson, M. Riverol, and J. T. Becker. 2014. Regular fish consumption and age-related brain gray matter loss. American Journal of Preventive Medicine 47 (4):444–51. doi: 10.1016/j.amepre.2014.05.037.
  • Regnier, M., A. Polizzi, S. Smati, C. Lukowicz, A. Fougerat, Y. Lippi, E. Fouche, F. Lasserre, C. Naylies, C. Betoulieres, et al. 2020. Hepatocyte-specific deletion of Pparα promotes NAFLD in the context of obesity. Scientific Reports 10 (1):6489. doi: 10.1038/s41598-020-63579-3.
  • Rice-Evans, C., and R. Burdon. 1993. Free radical-lipid interactions and their pathological consequences. Progress in Lipid Research 32 (1):71–110. doi: 10.1016/0163-7827(93)90006-I.
  • Rouault, T. A. 2009. Cell biology. An ancient gauge for iron. Science (New York, N.Y.) 326 (5953):676–7. doi: 10.1126/science.1181938.
  • Rouault, T. A., and S. Cooperman. 2006. Brain iron metabolism. Seminars in Pediatric Neurology 13 (3):142–8. doi: 10.1016/j.spen.2006.08.002.
  • Saboor, M., Zehra, A., and K. Qamar, Moinuddin. 2015. Disorders associated with malabsorption of iron: A critical review. Pakistan Journal of Medical Sciences 31 (6):1549–53. doi: 10.12669/pjms.316.8125.
  • Salminen, A., K. Kaarniranta, and A. Kauppinen. 2013. Crosstalk between oxidative stress and SIRT1: Impact on the aging process. International Journal of Molecular Sciences 14 (2):3834–59. doi: 10.3390/ijms14023834.
  • Samieri, C., P. Maillard, F. Crivello, C. Proust-Lima, E. Peuchant, C. Helmer, H. Amieva, M. Allard, J. F. Dartigues, S. C. Cunnane, et al. 2012. Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe. Neurology 79 (7):642–50. doi: 10.1212/WNL.0b013e318264e394.
  • Sazawal, S., R. E. Black, M. Ramsan, H. M. Chwaya, R. J. Stoltzfus, A. Dutta, U. Dhingra, I. Kabole, S. Deb, M. K. Othman, et al. 2006. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: Community-based, randomised, placebo-controlled trial. The Lancet 367 (9505):133–43. doi: 10.1016/S0140-6736(06)67962-2.
  • Schaer, C. A., F. Vallelian, A. Imhof, G. Schoedon, and D. J. Schaer. 2008. Heme carrier protein (HCP-1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation. Journal of Leukocyte Biology 83 (2):325–33. doi: 10.1189/jlb.0407226.
  • Schonfeld, E., I. Yasharel, E. Yavin, and A. Brand. 2007. Docosahexaenoic acid enhances iron uptake by modulating iron transporters and accelerates apoptotic death in PC12 cells. Neurochemical Research 32 (10):1673–84. doi: 10.1007/s11064-007-9378-x.
  • Seiler, A., M. Schneider, H. Forster, S. Roth, E. K. Wirth, C. Culmsee, N. Plesnila, E. Kremmer, O. Radmark, W. Wurst, et al. 2008. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metabolism 8 (3):237–48. doi: 10.1016/j.cmet.2008.07.005.
  • Sekiya, M., A. Hiraishi, M. Touyama, and K. Sakamoto. 2008. Oxidative stress induced lipid accumulation via SREBP1c activation in HepG2 cells. Biochemical and Biophysical Research Communications 375 (4):602–7. doi: 10.1016/j.bbrc.2008.08.068.
  • Shaikh, S. R., and M. Edidin. 2006. Polyunsaturated fatty acids, membrane organization, T cells, and antigen presentation. The American Journal of Clinical Nutrition 84 (6):1277–89. doi: 10.1093/ajcn/84.6.1277.
  • Shayeghi, M., G. O. Latunde-Dada, J. S. Oakhill, A. H. Laftah, K. Takeuchi, N. Halliday, Y. Khan, A. Warley, F. E. McCann, R. C. Hider, et al. 2005. Identification of an intestinal heme transporter. Cell 122 (5):789–801. doi: 10.1016/j.cell.2005.06.025.
  • Shchepinov, M. S., V. P. Chou, E. Pollock, J. W. Langston, C. R. Cantor, R. J. Molinari, and A. B. Manning-Boğ. 2011. Isotopic reinforcement of essential polyunsaturated fatty acids diminishes nigrostriatal degeneration in a mouse model of Parkinson's disease. Toxicology Letters 207 (2):97–103. doi: 10.1016/j.toxlet.2011.07.020.
  • She, H., S. Xiong, M. Lin, E. Zandi, C. Giulivi, and H. Tsukamoto. 2002. Iron activates NF-kappaB in Kupffer cells. American Journal of Physiology. Gastrointestinal and Liver Physiology 283 (3):G719–26. doi: 10.1152/ajpgi.00108.2002.
  • Sidiartha, I. G. L., I. M. Bakta, I. M. Wiryana, I. W. P. Sutirtayasa, and R. S. Damayanti. 2017. Eicosapentaenoic acid and docosahexaenoic acid in fish oil capsule supplementation in obese children decreases serum interleukin-6 and hepcidin and improves iron status. Bali Medical Journal 6 (1):97–101. doi: 10.15562/bmj.v6i1.410.
  • Singh, N., S. Haldar, A. K. Tripathi, K. Horback, J. Wong, D. Sharma, A. Beserra, S. Suda, C. Anbalagan, S. Dev, et al. 2014. Brain iron homeostasis: From molecular mechanisms to clinical significance and therapeutic opportunities. Antioxidants & Redox Signaling 20 (8):1324–63. doi: 10.1089/ars.2012.4931.
  • Smuts, C. M., J. Greeff, J. Kvalsvig, M. B. Zimmermann, and J. Baumgartner. 2015. Long-chain n-3 PUFA supplementation decreases physical activity during class time in iron-deficient South African school children. The British Journal of Nutrition 113 (2):212–24. doi: 10.1017/S0007114514003493.
  • Soemantri, A. G., E. Pollitt, and I. Kim. 1985. Iron deficiency anemia and educational achievement. The American Journal of Clinical Nutrition 42 (6):1221–8. doi: 10.1093/ajcn/42.6.1221.
  • Sofic, E., P. Riederer, H. Heinsen, H. Beckmann, G. P. Reynolds, G. Hebenstreit, and M. B. Youdim. 1988. Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. Journal of Neural Transmission 74 (3):199–205. doi: 10.1007/BF01244786.
  • Sorensen, L. B., C. T. Damsgaard, S. M. Dalskov, R. A. Petersen, N. Egelund, C. B. Dyssegaard, K. D. Stark, R. Andersen, I. Tetens, A. Astrup, et al. 2015. Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: Secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study. British Journal of Nutrition 114 (10):1623–37. doi: 10.1017/S0007114515003323.
  • Sorensen, L. B., C. B. Dyssegaard, C. T. Damsgaard, R. A. Petersen, S. M. Dalskov, M. F. Hjorth, R. Andersen, I. Tetens, C. Ritz, A. Astrup, et al. 2015. The effects of Nordic school meals on concentration and school performance in 8- to 11-year-old children in the OPUS School Meal Study: A cluster-randomised, controlled, cross-over trial. British Journal of Nutrition 113 (8):1280–91. doi: 10.1017/S0007114515000033.
  • Staroń, R., P. Lipiński, M. Lenartowicz, A. Bednarz, A. Gajowiak, E. Smuda, W. Krzeptowski, M. Pieszka, T. Korolonek, I. Hamza, et al. 2017. Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption. PLoS One 12 (7):e0181117. doi: 10.1371/journal.pone.0181117.
  • Starzyński, R. R., F. Canonne-Hergaux, M. Lenartowicz, W. Krzeptowski, A. Willemetz, A. Styś, J. Bierła, P. Pietrzak, T. Dziaman, and P. Lipiński. 2013. Ferroportin expression in haem oxygenase 1-deficient mice. Biochemical Journal 449 (1):69–78. doi: 10.1042/BJ20121139.
  • Stillwell, W., and S. R. Wassall. 2003. Docosahexaenoic acid: Membrane properties of a unique fatty acid. Chemistry and Physics of Lipids 126 (1):1–27. doi: 10.1016/S0009-3084(03)00101-4.
  • Stockwell, B. R., J. P. Friedmann Angeli, H. Bayir, A. I. Bush, M. Conrad, S. J. Dixon, S. Fulda, S. Gascón, S. K. Hatzios, V. E. Kagan, et al. 2017. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171 (2):273–85. doi: 10.1016/j.cell.2017.09.021.
  • Szudzik, M., R. Starzyński, A. Jończy, R. Mazgaj, M. Lenartowicz, and P. Lipiński. 2018. Iron supplementation in suckling piglets: An ostensibly easy therapy of neonatal iron deficiency anemia. Pharmaceuticals (Pharmaceuticals) 11 (4):128. doi: 10.3390/ph11040128.
  • Tabibi, H., M. Mirfatahi, M. Hedayati, and A. Nasrollahi. 2017. Effects of flaxseed oil on blood hepcidin and hematologic factors in hemodialysis patients. Hemodialysis International. International Symposium on Home Hemodialysis 21 (4):549–56. doi: 10.1111/hdi.12516.
  • Tan, G., L. Liu, Z. He, J. Sun, W. Xing, and X. Sun. 2016. Role of hepcidin and its downstream proteins in early brain injury after experimental subarachnoid hemorrhage in rats. Molecular and Cellular Biochemistry 418 (1–2):31–8. doi: 10.1007/s11010-016-2730-1.
  • Thirupathi, A., and Y. Z. Chang. 2019. Brain iron metabolism and CNS diseases. Advances in Experimental Medicine and Biology 1173:1–19. doi: 10.1007/978-981-13-9589-5_1.
  • Thorlaksdottir, A. Y., G. V. Skuladottir, A. L. Petursdottir, L. Tryggvadottir, H. M. Ogmundsdottir, J. E. Eyfjord, J. J. Jonsson, and I. Hardardottir. 2006. Positive association between plasma antioxidant capacity and n-3 PUFA in red blood cells from women. Lipids 41 (2):119–25. doi: 10.1007/s11745-006-5079-5.
  • Todorich, B., X. Zhang, and J. R. Connor. 2011. H-ferritin is the major source of iron for oligodendrocytes. Glia 59 (6):927–35. doi: 10.1002/glia.21164.
  • Todorich, B., X. Zhang, B. Slagle-Webb, W. E. Seaman, and J. R. Connor. 2008. Tim-2 is the receptor for H-ferritin on oligodendrocytes. Journal of Neurochemistry 107 (6):1495–505. doi: 10.1111/j.1471-4159.2008.05678.x.
  • Tolosano, E., and F. Altruda. 2002. Hemopexin: Structure, function, and regulation. DNA and Cell Biology 21 (4):297–306. doi: 10.1089/104454902753759717.
  • Tseng, P.-T., Y.-S. Cheng, C.-F. Yen, Y.-W. Chen, B. Stubbs, P. Whiteley, A. F. Carvalho, D.-J. Li, T.-Y. Chen, W.-C. Yang, et al. 2018. Peripheral iron levels in children with attention-deficit hyperactivity disorder: A systematic review and meta-analysis. Scientific Reports 8 (1):788. doi: 10.1038/s41598-017-19096-x.
  • Valenzuela, R., M. A. Rincon-Cervera, F. Echeverria, C. Barrera, A. Espinosa, M. C. Hernandez-Rodas, M. Ortiz, A. Valenzuela, and L. A. Videla. 2018. Iron-induced pro-oxidant and pro-lipogenic responses in relation to impaired synthesis and accretion of long-chain polyunsaturated fatty acids in rat hepatic and extrahepatic tissues. Nutrition (Burbank, Los Angeles County, Calif.) 45:49–58. doi: 10.1016/j.nut.2017.07.007.
  • Vessby, B., I. B. Gustafsson, S. Tengblad, M. Boberg, and A. Andersson. 2002. Desaturation and elongation of fatty acids and insulin action. Annals of the New York Academy of Sciences 967:183–95. doi: 10.1111/j.1749-6632.2002.tb04275.x.
  • Videla, L. A., and P. Pettinelli. 2012. Misregulation of PPAR functioning and its pathogenic consequences associated with nonalcoholic fatty liver disease in human obesity. PPAR Research 2012:107434. doi: 10.1155/2012/107434.
  • Videla, L. A., R. Rodrigo, J. Araya, and J. Poniachik. 2004. Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease. Free Radical Biology andMedicine 37 (9):1499–507. doi: 10.1016/j.freeradbiomed.2004.06.033.
  • Vulpe, C. D., Y. M. Kuo, T. L. Murphy, L. Cowley, C. Askwith, N. Libina, J. Gitschier, and G. J. Anderson. 1999. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nature Genetics 21 (2):195–9. doi: 10.1038/5979.
  • Wada, M., C. J. DeLong, Y. H. Hong, C. J. Rieke, I. Song, R. S. Sidhu, C. Yuan, M. Warnock, A. H. Schmaier, C. Yokoyama, et al. 2007. Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. The Journal of Biological Chemistry 282 (31):22254–66. doi: 10.1074/jbc.M703169200.
  • Waldron, K. J., J. C. Rutherford, D. Ford, and N. J. Robinson. 2009. Metalloproteins and metal sensing. Nature 460 (7257):823–30. doi: 10.1038/nature08300.
  • Waldvogel-Abramowski, S., G. Waeber, C. Gassner, A. Buser, B. M. Frey, B. Favrat, and J. D. Tissot. 2014. Physiology of iron metabolism. Transfusion Medicine and Hemotherapy : offizielles Organ Der Deutschen Gesellschaft Fur Transfusionsmedizin Und Immunhamatologie 41 (3):213–21. doi: 10.1159/000362888.
  • Wallace, D. F. 2016. The regulation of iron absorption and homeostasis. The Clinical Biochemist. Reviews 37 (2):51–62.
  • Walter, T. 2003. Effect of iron-deficiency anemia on cognitive skills and neuromaturation in infancy and childhood. Food and Nutrition Bulletin 24 (4 Suppl):S104–S10. doi: 10.1177/15648265030244S207.
  • Wang, C. Y., and J. L. Babitt. 2016. regulation in the anemia of inflammation. Current Opinion in Hematology 23 (3):189–97. doi: 10.1097/MOH.0000000000000236.
  • Wang, C. Y., and M. D. Knutson. 2013. Hepatocyte divalent metal-ion transporter-1 is dispensable for hepatic iron accumulation and non-transferrin-bound iron uptake in mice. Hepatology (Baltimore, Md.) 58 (2):788–98. doi: 10.1002/hep.26401.
  • Wang, Q., F. Du, Z.-M. Qian, X. H. Ge, L. Zhu, W. H. Yung, L. Yang, and Y. Ke. 2008. Lipopolysaccharide induces a significant increase in expression of iron regulatory hormone hepcidin in the cortex and substantia nigra in rat brain. Endocrinology 149 (8):3920–5. doi: 10.1210/en.2007-1626.
  • Weiland, A., Y. Wang, W. Wu, X. Lan, X. Han, Q. Li, and J. Wang. 2019. Ferroptosis and its role in diverse brain diseases. Molecular Neurobiology 56 (7):4880–93. doi: 10.1007/s12035-018-1403-3.
  • Weinberg, E. D. 1997. The Lactobacillus anomaly: Total iron abstinence. Perspectives in Biology and Medicine 40 (4):578–83. doi: 10.1353/pbm.1997.0072.
  • White, C., X. Yuan, P. J. Schmidt, E. Bresciani, T. K. Samuel, D. Campagna, C. Hall, K. Bishop, M. L. Calicchio, A. Lapierre, et al. 2013. HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. Cell Metabolism 17 (2):261–70. doi: 10.1016/j.cmet.2013.01.005.
  • WHO. 2017. "Nutritional anaemias: tools for effective prevention and control.” Geneva: World Health Organization, 13 November 2017. https://www.who.int/publications-detail/9789241513067.
  • Winterbourn, C. C. 1995. Toxicity of iron and hydrogen peroxide: The Fenton reaction. Toxicology Letters 82-83:969–74. doi: 10.1016/0378-4274(95)03532-X.
  • Witte, A. V., L. Kerti, H. M. Hermannstadter, J. B. Fiebach, S. J. Schreiber, J. P. Schuchardt, A. Hahn, and A. Floel. 2014. Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cerebral Cortex (New York, N.Y. : 1991) 24 (11):3059–68. doi: 10.1093/cercor/bht163.
  • Wong, B. X., and J. A. Duce. 2014. The iron regulatory capability of the major protein participants in prevalent neurodegenerative disorders. Frontiers in Pharmacology 5:81. doi: 10.3389/fphar.2014.00081.
  • Wong, B. X., A. Tsatsanis, L. Q. Lim, P. A. Adlard, A. I. Bush, and J. A. Duce. 2014. β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin. PLoS One 9 (12):e114174 doi: 10.1371/journal.pone.0114174.
  • Wu, L. J., A. G. Leenders, S. Cooperman, E. Meyron-Holtz, S. Smith, W. Land, R. Y. Tsai, U. V. Berger, Z. H. Sheng, and T. A. Rouault. 2004. Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier. Brain Research 1001 (1–2):108–17. doi: 10.1016/j.brainres.2003.10.066.
  • Wu, Y., A. Baylin, and J. A. Colacino. 2018. Iron, oxidative stress, and Δ9 Stearoyl-CoenzymeA Desaturase Index (C16:1/C16:0): An analysis applying the national health and nutrition examination survey 2003-04. Current Developments in Nutrition 2 (1):1–8. doi: 10.1093/cdn/nzx001.
  • Xiaoli, A. M., Z. Song, and F. Yang. 2019. Lipogenic SREBP-1a/c transcription factors activate expression of the iron regulator hepcidin, revealing cross-talk between lipid and iron metabolisms. The Journal of Biological Chemistry 294 (34):12743–53. doi: 10.1074/jbc.RA119.009644.
  • Xie, Y., W. Hou, X. Song, Y. Yu, J. Huang, X. Sun, R. Kang, and D. Tang. 2016. Ferroptosis: Process and function. Cell Death and Differentiation 23 (3):369–79. doi: 10.1038/cdd.2015.158.
  • Xiong, X.-Y., L. Liu, F.-X. Wang, Y.-R. Yang, J.-W. Hao, P.-F. Wang, Q. Zhong, K. Zhou, A. Xiong, W.-Y. Zhu, et al. 2016. Toll-like receptor 4/MyD88-mediated signaling of hepcidin expression causing brain iron accumulation, oxidative injury, and cognitive impairment after intracerebral hemorrhage. Circulation 134 (14):1025–38. doi: 10.1161/CIRCULATIONAHA.116.021881.
  • Yehuda, S., S. Rabinovitz, R. L. Carasso, and D. I. Mostofsky. 2002. The role of polyunsaturated fatty acids in restoring the aging neuronal membrane. Neurobiology of Aging 23 (5):843–53. doi: 10.1016/S0197-4580(02)00074-X.
  • Yehuda, S., S. Rabinovitz, R. L. Carasso, and D. I. Mostofsky. 2008. Long-lasting cognitive, physiological and hematological effects in rehabilitated, early dietary iron-deficiency adult rats, and improvement by treatment with a mixture of essential fatty acids. Nutritional Neuroscience 11 (4):167–71. doi: 10.1179/147683008X301568.
  • Yehuda, S., S. Rabinovitz, and D. I. Mostofsky. 2005. Essential fatty acids and the brain: From infancy to aging. Neurobiology of Aging 26 Suppl 1 (Suppl 1):98–102. doi: 10.1016/j.neurobiolaging.2005.09.013.
  • Yiannikourides, A., and G. O. Latunde-Dada. 2019. A short review of iron metabolism and pathophysiology of iron disorders. Medicines (Medicines) 6 (3):85. doi: 10.3390/medicines6030085.
  • Zhang, D. L., T. Senecal, M. C. Ghosh, H. Ollivierre-Wilson, T. Tu, and T. A. Rouault. 2011. Hepcidin regulates ferroportin expression and intracellular iron homeostasis of erythroblasts. Blood 118 (10):2868–77. doi: 10.1182/blood-2011-01-330241.
  • Zuniga, J., M. Cancino, F. Medina, P. Varela, R. Vargas, G. Tapia, L. A. Videla, and V. Fernandez. 2011. N-3 PUFA supplementation triggers PPAR-α activation and PPAR-α/NF-κB interaction: Anti-inflammatory implications in liver ischemia-reperfusion injury. PLoS One 6 (12):e28502. doi: 10.1371/journal.pone.0028502.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.