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Pharmaceuticals (Basel). 2018 Oct 22;11(4). doi: 10.3390/ph11040113.

Links Between Iron and Lipids: Implications in Some Major Human Diseases.

Pharmaceuticals (Basel, Switzerland)

Stephanie Rockfield, Ravneet Chhabra, Michelle Robertson, Nabila Rehman, Richa Bisht, Meera Nanjundan

Affiliations

  1. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 336200, USA. [email protected].
  2. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 336200, USA. [email protected].
  3. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 336200, USA. [email protected].
  4. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 336200, USA. [email protected].
  5. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 336200, USA. [email protected].
  6. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 336200, USA. [email protected].

PMID: 30360386 PMCID: PMC6315991 DOI: 10.3390/ph11040113

Abstract

Maintenance of iron homeostasis is critical to cellular health as both its excess and insufficiency are detrimental. Likewise, lipids, which are essential components of cellular membranes and signaling mediators, must also be tightly regulated to hinder disease progression. Recent research, using a myriad of model organisms, as well as data from clinical studies, has revealed links between these two metabolic pathways, but the mechanisms behind these interactions and the role these have in the progression of human diseases remains unclear. In this review, we summarize literature describing cross-talk between iron and lipid pathways, including alterations in cholesterol, sphingolipid, and lipid droplet metabolism in response to changes in iron levels. We discuss human diseases correlating with both iron and lipid alterations, including neurodegenerative disorders, and the available evidence regarding the potential mechanisms underlying how iron may promote disease pathogenesis. Finally, we review research regarding iron reduction techniques and their therapeutic potential in treating patients with these debilitating conditions. We propose that iron-mediated alterations in lipid metabolic pathways are involved in the progression of these diseases, but further research is direly needed to elucidate the mechanisms involved.

Keywords: cancer; iron; iron chelation; lipid; neurodegeneration; obesity; phlebotomy

References

  1. N Engl J Med. 1999 Dec 23;341(26):1986-95 - PubMed
  2. Diabetes. 2002 Apr;51(4):1000-4 - PubMed
  3. J Biol Chem. 2004 Jul 2;279(27):28614-24 - PubMed
  4. Exp Neurol. 2004 Dec;190(2):506-14 - PubMed
  5. Int J Biochem Cell Biol. 2005 Jun;37(6):1173-8 - PubMed
  6. FEBS Lett. 2005 Oct 24;579(25):5571-6 - PubMed
  7. Am J Clin Nutr. 2006 Feb;83(2):461S-465S - PubMed
  8. Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13612-7 - PubMed
  9. J Nutr. 2007 Nov;137(11):2366-70 - PubMed
  10. Transfusion. 2007 Nov;47(11):2017-24 - PubMed
  11. Clin Cancer Res. 2008 Jan 1;14(1):32-40 - PubMed
  12. J Natl Cancer Inst. 2008 Apr 16;100(8):572-9 - PubMed
  13. Am J Clin Nutr. 2008 May;87(5):1374-83 - PubMed
  14. Biochim Biophys Acta. 2009 Jul;1790(7):702-17 - PubMed
  15. Proc Natl Acad Sci U S A. 2008 May 27;105(21):7410-5 - PubMed
  16. Science. 2008 May 30;320(5880):1207-10 - PubMed
  17. J Natl Cancer Inst. 2008 Jul 16;100(14):996-1002 - PubMed
  18. Gynecol Endocrinol. 2009 Jan;25(1):39-52 - PubMed
  19. Future Lipidol. 2007 Apr;2(2):229-237 - PubMed
  20. Cell Cycle. 2009 Nov 15;8(22):3695-701 - PubMed
  21. Crit Rev Biochem Mol Biol. 2010 Jun;45(3):185-98 - PubMed
  22. J Biochem. 2010 Jul;148(1):13-24 - PubMed
  23. Curr Opin Clin Nutr Metab Care. 2010 Jul;13(4):371-6 - PubMed
  24. Hepatology. 2010 Aug;52(2):462-71 - PubMed
  25. Acta Neurol Scand. 2011 Nov;124(5):295-301 - PubMed
  26. Biochem J. 2011 Mar 15;434(3):365-81 - PubMed
  27. Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3):null - PubMed
  28. Hum Reprod. 2011 Sep;26(9):2262-73 - PubMed
  29. Biochim Biophys Acta. 2012 Mar;1820(3):403-10 - PubMed
  30. J Biol Chem. 2011 Oct 14;286(41):36053-62 - PubMed
  31. Adv Nutr. 2011 Mar;2(2):112-21 - PubMed
  32. Annu Rev Biochem. 2012;81:687-714 - PubMed
  33. BMC Med. 2012 May 30;10:54 - PubMed
  34. J Biomol Struct Dyn. 2012;30(4):394-406 - PubMed
  35. Neurobiol Aging. 2013 Feb;34(2):562-75 - PubMed
  36. Cell Metab. 2012 Jul 3;16(1):90-6 - PubMed
  37. J Biol Chem. 2012 Oct 5;287(41):34032-43 - PubMed
  38. Mol Cell Neurosci. 2013 Jul;55:50-61 - PubMed
  39. J Biol Chem. 2013 Jan 18;288(3):1696-705 - PubMed
  40. J Biomol Struct Dyn. 2014;32(1):155-69 - PubMed
  41. Haematologica. 2013 Jul;98(7):1049-57 - PubMed
  42. Obes Rev. 2013 Oct;14(10):771-9 - PubMed
  43. Biochim Biophys Acta. 2014 Apr;1837(4):408-17 - PubMed
  44. Hum Reprod. 2014 Mar;29(3):577-83 - PubMed
  45. J Am Chem Soc. 2014 Mar 26;136(12):4551-6 - PubMed
  46. Nature. 2014 May 1;509(7498):105-9 - PubMed
  47. J Res Med Sci. 2014 Feb;19(2):164-74 - PubMed
  48. Front Aging Neurosci. 2014 Jun 12;6:121 - PubMed
  49. J Am Chem Soc. 2014 Oct 15;136(41):14554-9 - PubMed
  50. Nat Cell Biol. 2014 Nov;16(11):1069-79 - PubMed
  51. Nat Rev Mol Cell Biol. 2015 Jan;16(1):45-55 - PubMed
  52. Nutrients. 2015 Jan 06;7(1):335-48 - PubMed
  53. Crit Rev Food Sci Nutr. 2016;56(6):1012-20 - PubMed
  54. Biochim Biophys Acta. 2015 May;1853(5):1130-44 - PubMed
  55. Curr Opin Cell Biol. 2015 Apr;33:125-31 - PubMed
  56. Nutrients. 2015 Mar 31;7(4):2274-96 - PubMed
  57. ACS Chem Biol. 2015 Jul 17;10(7):1604-9 - PubMed
  58. Nat Commun. 2015 May 19;6:6760 - PubMed
  59. Nat Rev Neurol. 2015 Jul;11(7):369 - PubMed
  60. Trends Cell Biol. 2016 Mar;26(3):165-176 - PubMed
  61. Neurochem Res. 2016 Feb;41(1-2):243-57 - PubMed
  62. Neurobiol Dis. 2016 Mar;87:59-68 - PubMed
  63. Cell Death Differ. 2016 Mar;23(3):369-79 - PubMed
  64. PLoS One. 2016 Jan 25;11(1):e0147474 - PubMed
  65. Ann N Y Acad Sci. 2016 Mar;1368(1):149-61 - PubMed
  66. J Alzheimers Dis. 2016;51(2):471-87 - PubMed
  67. Genetics. 2016 May;203(1):241-53 - PubMed
  68. J Trace Elem Med Biol. 2016 Dec;38:81-92 - PubMed
  69. Elife. 2016 Jun 25;5: - PubMed
  70. Nat Rev Cancer. 2016 Oct;16(10):619-34 - PubMed
  71. Biochem Biophys Res Commun. 2016 Sep 16;478(2):838-44 - PubMed
  72. Biochem Biophys Res Commun. 2016 Sep 23;478(3):1338-43 - PubMed
  73. J Mol Neurosci. 2016 Nov;60(3):325-335 - PubMed
  74. Nat Chem Biol. 2017 Jan;13(1):91-98 - PubMed
  75. Biometals. 2017 Feb;30(1):1-16 - PubMed
  76. Elife. 2016 Nov 30;5: - PubMed
  77. Biochim Biophys Acta Mol Cell Res. 2017 Feb;1864(2):399-430 - PubMed
  78. Biol Chem. 2017 Aug 28;398(9):995-1007 - PubMed
  79. Front Cell Dev Biol. 2017 Jan 10;4:154 - PubMed
  80. Redox Biol. 2017 Aug;12:8-17 - PubMed
  81. Clin Biochem Rev. 2016 May;37(2):51-62 - PubMed
  82. Oncogene. 2017 Jul 20;36(29):4089-4099 - PubMed
  83. Cancer Lett. 2017 Aug 10;401:39-45 - PubMed
  84. J Alzheimers Dis. 2017;58(4):1109-1119 - PubMed
  85. Curr Opin Chem Biol. 2017 Aug;39:83-89 - PubMed
  86. Sci Rep. 2017 Jul 14;7(1):5495 - PubMed
  87. Theranostics. 2017 Jul 23;7(13):3293-3305 - PubMed
  88. Biochem Biophys Res Commun. 2018 Jan 1;495(1):1548-1554 - PubMed
  89. Nat Rev Mol Cell Biol. 2018 Mar;19(3):175-191 - PubMed
  90. Sci Rep. 2018 Jan 12;8(1):574 - PubMed
  91. FEBS Lett. 2018 Feb;592(3):394-401 - PubMed
  92. Mediators Inflamm. 2017;2017:9173090 - PubMed
  93. J Nutr. 2018 Feb 1;148(2):174-184 - PubMed
  94. J Biol Chem. 2018 May 25;293(21):8297-8311 - PubMed
  95. Biochem Biophys Res Commun. 2018 Apr 30;499(1):44-51 - PubMed
  96. J Biol Chem. 2018 May 25;293(21):8312-8313 - PubMed
  97. J Alzheimers Dis. 2018;64(s1):S379-S395 - PubMed
  98. OMICS. 2018 Jul;22(7):502-513 - PubMed
  99. Molecules. 2018 Aug 03;23(8):null - PubMed
  100. Cell Mol Gastroenterol Hepatol. 2018 Apr 16;6(2):215-217.e8 - PubMed
  101. Metallomics. 2018 Sep 19;10(9):1307-1314 - PubMed
  102. J Mol Neurosci. 2018 Oct;66(2):197-206 - PubMed
  103. J Cell Physiol. 2019 Feb;234(2):1111-1129 - PubMed
  104. Free Radic Biol Med. 2018 Sep 12;:null - PubMed
  105. Free Radic Biol Med. 2018 Sep 25;:null - PubMed
  106. Proc Natl Acad Sci U S A. 1987 May;84(10):3457-61 - PubMed
  107. J Biol Chem. 1984 Dec 10;259(23):14354-6 - PubMed
  108. J Pathol. 1995 Sep;177(1):83-94 - PubMed
  109. Toxicol Lett. 1995 Dec;82-83:969-74 - PubMed

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