Prostaglandins, Leukotrienes and Essential Fatty Acids
Volume 80, Issue 2 , Pages 157-163 , February 2009

Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study

  • Chuck T. Chen

      Affiliations

    • Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, Ontario, Canada M5S 3E2
    • Corresponding Author InformationCorresponding author.
  • ,
  • Zhen Liu

      Affiliations

    • Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, Ontario, Canada M5S 3E2
  • ,
  • Melissa Ouellet

      Affiliations

    • Faculty of Pharmacy, Laval University and Molecular Endocrinology and Oncology Research Center, Centre Hospitalier de l’Université Laval (CHUL) Research Center, 2705 Boulevard Laurier, Québec, Canada G1V 4G2
  • ,
  • Frédéric Calon

      Affiliations

    • Faculty of Pharmacy, Laval University and Molecular Endocrinology and Oncology Research Center, Centre Hospitalier de l’Université Laval (CHUL) Research Center, 2705 Boulevard Laurier, Québec, Canada G1V 4G2
    • These laboratories contributed equally to this work.
    • Tel.: +14186542296.
  • ,
  • Richard P. Bazinet

      Affiliations

    • Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, Ontario, Canada M5S 3E2
    • These laboratories contributed equally to this work.
    • Tel.: +14169468276; fax: +14169785882.

Received 10 October 2008 ,Revised 5 December 2008 ,Accepted 8 January 2009.

Reference 

  1. Scott BL, Bazan NG. Membrane docosahexaenoate is supplied to the developing brain and retina by the liver. Proc. Natl. Acad. Sci. USA. 1989;86:2903–2907
  2. Cunnane SC. Problems with essential fatty acids: time for a new paradigm?. Prog. Lipid Res. 2003;42:544–568
  3. Voss A, Reinhart M, Sankarappa S, Sprecher H. The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase. J. Biol. Chem. 1991;266:19995–20000
  4. Serhan CN, Clish CB, Brannon J, et al. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J. Exp. Med. 2000;192:1197–1204
  5. Serhan CN, Clish CB, Brannon J, et al. Anti-microinflammatory lipid signals generated from dietary N-3 fatty acids via cyclooxygenase-2 and transcellular processing: a novel mechanism for NSAID and N-3 PUFA therapeutic actions. J. Physiol. Pharmacol. 2000;51:643–654
  6. Serhan CN, Hong S, Gronert K, et al. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med. 2002;196:1025–1037
  7. Black KL, Hoff JT, Radin NS, Deshmukh GD. Eicosapentaenoic acid: effect on brain prostaglandins, cerebral blood flow and edema in ischemic gerbils. Stroke. 1984;15:65–69
  8. Song C, Manku MS, Horrobin DF. Long-chain polyunsaturated fatty acids modulate interleukin-1beta-induced changes in behavior, monoaminergic neurotransmitters, and brain inflammation in rats. J. Nutr. 2008;138:954–963
  9. Song C, Phillips AG, Leonard BE, Horrobin DF. Ethyl-eicosapentaenoic acid ingestion prevents corticosterone-mediated memory impairment induced by central administration of interleukin-1beta in rats. Mol. Psychiatry. 2004;9:630–638
  10. Kew S, Wells S, Thies F, et al. The effect of eicosapentaenoic acid on rat lymphocyte proliferation depends upon its position in dietary triacylglycerols. J. Nutr. 2003;133:4230–4238
  11. Miles EA, Banerjee T, Dooper MM, et al. The influence of different combinations of gamma-linolenic acid, stearidonic acid and EPA on immune function in healthy young male subjects. Br. J. Nutr. 2004;91:893–903
  12. Peterson LD, Jeffery NM, Thies F, et al. 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. 1998;33:171–180
  13. Thies F, Nebe-von-Caron G, Powell JR, et al. Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55y. Am. J. Clin. Nutr. 2001;73:539–548
  14. Adan Y, Shibata K, Sato M, Ikeda I, Imaizumi K. Effects of docosahexaenoic and eicosapentaenoic acid on lipid metabolism, eicosanoid production, platelet aggregation and atherosclerosis in hypercholesterolemic rats. Biosci. Biotechnol. Biochem. 1999;63:111–119
  15. Ahmed AA, Holub BJ. Alteration and recovery of bleeding times, platelet aggregation and fatty acid composition of individual phospholipids in platelets of human subjects receiving a supplement of cod-liver oil. Lipids. 1984;19:617–624
  16. Nieuwenhuys CM, Hornstra G. The effects of purified eicosapentaenoic and docosahexaenoic acids on arterial thrombosis tendency and platelet function in rats. Biochim. Biophys. Acta. 1998;390:313–322
  17. Park Y, Harris W. EPA, but not DHA, decreases mean platelet volume in normal subjects. Lipids. 2002;37:941–946
  18. Turini ME, Powell WS, Behr SR, Holub BJ. Effects of a fish-oil and vegetable-oil formula on aggregation and ethanolamine-containing lysophospholipid generation in activated human platelets and on leukotriene production in stimulated neutrophils. Am. J. Clin. Nutr. 1994;60:717–724
  19. Black KL, Hsu S, Radin NS, Hoff JT. Effect of intravenous eicosapentaenoic acid on cerebral blood flow, edema and brain prostaglandins in ischemic gerbils. Prostaglandins. 1984;28:545–556
  20. Katayama Y, Katsumata T, Muramatsu H, et al. Effect of long-term administration of ethyl eicosapentate (EPA-E) on local cerebral blood flow and glucose utilization in stroke-prone spontaneously hypertensive rats (SHRSP). Brain Res. 1997;761:300–305
  21. Katsumata T, Katayama Y, Obo R, et al. Delayed administration of ethyl eicosapentate improves local cerebral blood flow and metabolism without affecting infarct volumes in the rat focal ischemic model. Eur. J. Pharmacol. 1999;372:167–174
  22. Chen CT, Ma DW, Kim JH, Mount HT, Bazinet RP. The low density lipoprotein receptor is not necessary for maintaining mouse brain polyunsaturated fatty acid concentrations. J. Lipid. Res. 2008;49:147–152
  23. DeMar JC, DiMartino C, Baca AW, Lefkowitz W, Salem N. Effect of dietary docosahexaenoic acid on biosynthesis of docosahexaenoic acid from alpha-linolenic acid in young rats. J. Lipid. Res. 2008;49:1963–1980
  24. Philbrick DJ, Mahadevappa VG, Ackman RG, Holub BJ. Ingestion of fish oil or a derived n-3 fatty acid concentrate containing eicosapentaenoic acid (EPA) affects fatty acid compositions of individual phospholipids of rat brain, sciatic nerve and retina. J. Nutr. 1987;117:1663–1670
  25. Edmond J. Essential polyunsaturated fatty acids and the barrier to the brain: the components of a model for transport. J. Mol. Neurosci. 2001;16:181–193(Discussion 215-121)
  26. Spector AA. Plasma free fatty acid and lipoproteins as sources of polyunsaturated fatty acid for the brain. J. Mol. Neurosci. 2001;16:159–165(Discussion 215-121)
  27. Hamilton JA, Brunaldi K. A model for fatty acid transport into the brain. J. Mol. Neurosci. 2007;33:12–17
  28. Hamilton JA, Johnson RA, Corkey B, Kamp F. Fatty acid transport: the diffusion mechanism in model and biological membranes. J. Mol. Neurosci. 2001;16:99–108discussion 151-107
  29. Rapoport SI, Chang MC, Spector AA. Delivery and turnover of plasma-derived essential PUFAs in mammalian brain. J. Lipid Res. 2001;42:678–685
  30. Edmond J, Higa TA, Korsak RA, Bergner EA, Lee WN. Fatty acid transport and utilization for the developing brain. J. Neurochem. 1998;70:1227–1234
  31. Innis SM, Sprecher H, Hachey D, Edmond J, Anderson RE. Neonatal polyunsaturated fatty acid metabolism. Lipids. 1999;34:139–149
  32. Marbois BN, Ajie HO, Korsak RA, Sensharma DK, Edmond J. The origin of palmitic acid in brain of the developing rat. Lipids. 1992;27:587–592
  33. Igarashi M, DeMar JC, Ma K, et al. Docosahexaenoic acid synthesis from alpha-linolenic acid by rat brain is unaffected by dietary n-3 PUFA deprivation. J. Lipid Res. 2007;48:1150–1158
  34. Hanaka S, Abe T, Itakura H, Matsumoto A. Gene expression related to cholesterol metabolism in mouse brain during development. Brain Dev. 2000;22:321–326
  35. Hofmann SL, Russell DW, Goldstein JL, Brown MS. mRNA for low density lipoprotein receptor in brain and spinal cord of immature and mature rabbits. Proc. Natl. Acad. Sci. USA. 1987;84:6312–6316
  36. Meresse S, Delbart C, Fruchart JC, Cecchelli R. Low-density lipoprotein receptor on endothelium of brain capillaries. J. Neurochem. 1989;53:340–345
  37. Lein ES, Hawrylycz MJ, Ao N, et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature. 2007;445:168–176
  38. Ricciarelli R, D’Abramo C, Zingg JM, et al. CD36 overexpression in human brain correlates with beta-amyloid deposition but not with Alzheimer's disease. Free Radical Biol. Med. 2004;36:1018–1024
  39. Kamp F, Hamilton JA. pH gradients across phospholipid membranes caused by fast flip-flop of un-ionized fatty acids. Proc. Natl. Acad. Sci. USA. 1992;89:11367–11370
  40. Kamp F, Zakim D, Zhang F, Noy N, Hamilton JA. Fatty acid flip-flop in phospholipid bilayers is extremely fast. Biochemistry. 1995;34:11928–11937
  41. Demar JC, Ma K, Chang L, Bell JM, Rapoport SI. alpha-Linolenic acid does not contribute appreciably to docosahexaenoic acid within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic acid. J. Neurochem. 2005;94:1063–1076
  42. DeMar JC, Lee HJ, Ma K, et al. Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats. Biochim. Biophys. Acta. 2006;1761:1050–1059
  43. Golovko MY, Murphy EJ. Uptake and metabolism of plasma-derived erucic acid by rat brain. J. Lipid Res. 2006;47:1289–1297
  44. Smith QR, Nagura H. Fatty acid uptake and incorporation in brain: studies with the perfusion model. J. Mol. Neurosci. 2001;16:167–172(Discussion 215-121)
  45. Takasato Y, Rapoport SI, Smith QR. An in situ brain perfusion technique to study cerebrovascular transport in the rat. Am. J. Physiol. 1984;247:H484–H493
  46. Dagenais C, Rousselle C, Pollack GM, Scherrmann JM. Development of an in situ mouse brain perfusion model and its application to mdr1a P-glycoprotein-deficient mice. J. Cereb. Blood Flow Metab. 2000;20:381–386
  47. Green JT, Orr SK, Bazinet RP. The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids. J. Lipid Res. 2008;49:939–944
  48. Chen CT, Green JT, Orr SK, Bazinet RP. Regulation of brain polyunsaturated fatty acid uptake and turnover. Prostaglandins Leukot. Essent. Fatty Acids. 2008;79:85–91
  49. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 1957;226:497–509
  50. Miller JC, Gnaedinger JM, Rapoport SI. Utilization of plasma fatty acid in rat brain: distribution of [14C]palmitate between oxidative and synthetic pathways. J. Neurochem. 1987;49:1507–1514
  51. Igarashi M, DeMar JC, Ma K, et al. Upregulated liver conversion of alpha-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet. J. Lipid Res. 2007;48:152–164
  52. Sublette ME, Bosetti F, DeMar JC, et al. Plasma free polyunsaturated fatty acid levels are associated with symptom severity in acute mania. Bipolar Disord. 2007;9:759–765
  53. Gavino GR, Gavino VC. Rat liver outer mitochondrial carnitine palmitoyltransferase activity towards long-chain polyunsaturated fatty acids and their CoA esters. Lipids. 1991;26:266–270
  54. Oldendorf WH, Brown WJ. Greater number of capillary endothelial cell mitochondria in brain than in muscle. Proc. Soc. Exp. Biol. Med. 1975;149:736–738
  55. Oldendorf WH, Cornford ME, Brown WJ. The large apparent metabolic work capacity of the blood–brain barrier. Trans. Am. Neurol. Assoc. 1976;101:157–160
  56. Oldendorf WH, Cornford ME, Brown WJ. The large apparent work capability of the blood–brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann. Neurol. 1977;1:409–417
  57. Stewart PA, Wiley MJ. Structural and histochemical features of the avian blood–brain barrier. J. Comp. Neurol. 1981;202:157–167
  58. Bazinet RP, Rao JS, Chang L, Rapoport SI, Lee HJ. Chronic carbamazepine decreases the incorporation rate and turnover of arachidonic acid but not docosahexaenoic acid in brain phospholipids of the unanesthetized rat: relevance to bipolar disorder. Biol. Psychiatry. 2006;59:401–407
  59. Bazinet RP, Rao JS, Chang L, Rapoport SI, Lee HJ. Chronic valproate does not alter the kinetics of docosahexaenoic acid within brain phospholipids of the unanesthetized rat. Psychopharmacol. (Berl.). 2005;182:180–185
  60. Lee HJ, Ghelardoni S, Chang L, et al. Topiramate does not alter the kinetics of arachidonic or docosahexaenoic acid in brain phospholipids of the unanesthetized rat. Neurochem. Res. 2005;30:677–683
  61. Ge L, Gordon JS, Hsuan C, Stenn K, Prouty SM. Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity. J. Invest. Dermatol. 2003;120:707–714
  62. Bourre JM, Piciotti M. Delta-6 desaturation of alpha-linolenic acid in brain and liver during development and aging in the mouse. Neurosci. Lett. 1992;141:65–68
  63. Bourre JM, Piciotti M, Dumont O. Delta 6 desaturase in brain and liver during development and aging. Lipids. 1990;25:354–356
  64. Cunnane SC, Ryan MA, Lin YH, Lim SY, Salem N. Suckling rats actively recycle carbon from alpha-linolenate into newly synthesized lipids even during extreme dietary deficiency of n-3 polyunsaturates. Pediatr. Res. 2006;59:107–110
  65. Menard CR, Goodman KJ, Corso TN, Brenna JT, Cunnane SC. Recycling of carbon into lipids synthesized de novo is a quantitatively important pathway of alpha-[U-13C]linolenate utilization in the developing rat brain. J. Neurochem. 1998;71:2151–2158
  66. Taha AY, Ryan MA, Cunnane SC. Markedly raised intake of saturated and monounsaturated fatty acids in rats on a high-fat ketogenic diet does not inhibit carbon recycling of 13C-alpha-linolenate. Lipids. 2006;41:933–935
  67. Murphy CC, Murphy EJ, Golovko MY. Erucic acid is differentially taken up and metabolized in rat liver and heart. Lipids. 2008;43:391–400
  68. Cunnane SC, Ryan MA, Nadeau CR, et al. Why is carbon from some polyunsaturates extensively recycled into lipid synthesis?. Lipids. 2003;38:477–484
  69. Berridge MJ, Downes CP, Hanley MR. Neural and developmental actions of lithium: a unifying hypothesis. Cell. 1989;59:411–419
  70. Ding D, Greenberg ML. Lithium and valproate decrease the membrane phosphatidylinositol/phosphatidylcholine ratio. Mol. Microbiol. 2003;47:373–381
  71. Jope RS, Song L, Li PP, et al. The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain. J. Neurochem. 1996;66:2402–2409
  72. O’Donnell T, Rotzinger S, Nakashima TT, et al. Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in rat brain. Brain Res. 2000;880:84–91
  73. Silverstone PH, Wu RH, O’Donnell T, et al. Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients. Hum. Psychopharmacol. 2002;17:321–327
  74. Frangou S, Lewis M, McCrone P. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br. J. Psychiatry. 2006;188:46–50
  75. Frangou S, Lewis M, Wollard J, Simmons A. Preliminary in vivo evidence of increased N-acetyl-aspartate following eicosapentanoic acid treatment in patients with bipolar disorder. J. Psychopharmacol. 2007;21:435–439
  76. Lee HC, Inoue T, Imae R, et al. Caenorhabditis elegans mboa-7, a member of the MBOAT family, is required for selective incorporation of polyunsaturated fatty acids into phosphatidylinositol. Mol. Biol. Cell. 2008;19:1174–1184
  77. Rumsey SC, Galeano NF, Lipschitz B, Deckelbaum RJ. Oleate and other long chain fatty acids stimulate low density lipoprotein receptor activity by enhancing acyl coenzyme A:cholesterol acyltransferase activity and altering intracellular regulatory cholesterol pools in cultured cells. J. Biol. Chem. 1995;270:10008–10016
  78. Bazinet RP, Douglas H, McMillan EG, Wilkie BN, Cunnane SC. Intramuscular injection of antigens and adjuvant preferentially decreases 18:2n-6 and 18:3n-3 in pig neck muscle. Lipids. 2003;38:1221–1226
  79. Chicco AJ, Sparagna GC. Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am. J. Physiol. 2007;292:C33–C44

PII: S0952-3278(09)00003-9

doi: 10.1016/j.plefa.2009.01.005

Prostaglandins, Leukotrienes and Essential Fatty Acids
Volume 80, Issue 2 , Pages 157-163 , February 2009