Skip to main content
SpringerLink
Log in

Long-chain polyunsaturated fatty acids

Metabolism, physiology and clinical significance

  • Chapter
A Perinatal Strategy For Preventing Adult Disease: The Role Of Long-Chain Polyunsaturated Fatty Acids

  • 75 Accesses

Abstract

Long-chain polyunsaturated fatty acids (LCPUFAs) are derived from essential fatty acids (EFAs). EFAs cannot be made by the body and are essential nutrients. Hence they have to be obtained exogenously, as they are needed for cell membrane structure and as precursors of various eicosanoids1. It should be understood here that in the literature the terms EFAs, PUFAs (polyunsaturated fatty acids) and LCPUFAs are used sometimes interchangeably though they denote different types of fatty acids. For instance, linoleic acid (LA, 18:2 ω-6) and α-linolenic acid (ALA, 18:3 ω-3) are EFAs, whereas γ-linolenic acid (GLA, 18:3 ω-6), dihomo-GLA (DGLA, 20:3 ω-6), arachidonic acid (AA, 20:4 ω-6), eicosapentaenoic acid (EPA, 20:5 ω-3), docosapentaenoic acid (DPA, 22:5 ω-3), and docosahexaenoic acid (DHA, 22:6 ω-3) are PUFAs and are non-essential fatty acids. AA, EPA, DPA, and DHA are also called as LCPUFAs. Many times, more for the sake of convenience, LA, GLA, DGLA, AA, ALA, EPA, DPA, and DHA are collectively called as EFAs or PUFAs, though in strict sense this is not correct. Here the word LCPUFAs refers to AA, EPA, DPA, and DHA; the word EFAs stands for LA and ALA whereas PUFAs is used to denote GLA, DGLA, AA, EPA, DPA, and DHA. It should also be understood that EFAs are also PUFAs (since they contain 2 or more double bonds) but all PUFAs are not EFAs (reviewed in 1).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Das UN, Horrobin DF, Begin ME, et al. Clinical significance of essential fatty acids. Nutrition 1988; 4: 337–341.

    CAS  Google Scholar 

  2. Berger A, Crozier G, Bisogno T, Cavaliere P, Innis S, DiMarzo V. Anandamide and diet: Inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets. Proc Natl Acad Sci USA 2001; 98: 6402–6406.

    Article  PubMed  CAS  Google Scholar 

  3. DiMarzo V, Gopraraju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001; 410: 822–825.

    Article  CAS  Google Scholar 

  4. Huang SM, Bisogno T, Petros TJ, et al. Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain. J Biol Chem 2001; 276: 42639–42644.

    Article  PubMed  CAS  Google Scholar 

  5. Coles B, Bloodsworth A, Eiserich JP, et al. Nitrolinoleate inhibits platelet activation by attenuating calcium mobilization and inducing phosphorylation of vasodilator-stimulated phosphoprotein (VASP) through elevation of cAMP. J Biol Chem, in press.

    Google Scholar 

  6. Stone KJ, Willis AL, Hart M et al. The metabolism of dihomogammalinolenic acid in man. Lipids 1979; 14: 174–180.

    Article  PubMed  CAS  Google Scholar 

  7. Das UN. Atherosclerosis and prostaglandins. Int J Tissue React 1982; 4: 127–132.

    PubMed  CAS  Google Scholar 

  8. Das UN. Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot Essen Fatty Acids 2000; 63: 351–362.

    Article  CAS  Google Scholar 

  9. Klockenbusch W, Goecke TW, Krussel JS, Tutschek BA, Crombach G, Schror K. Prostacyclin deficiency and reduced fetoplacental blood flow in pregnancy-induced hypertension and preeclampsia. Gynecol Obstet Invest 2000; 50: 103–107.

    Article  PubMed  CAS  Google Scholar 

  10. Malatyalioglu E, Adam B, Yanik FF, Kokcu A, Alvur M. Levels of stable metabolites of prostacyclin and thromboxane A2 and their ratio in normotensive and preeclamptic pregnant women during the antepartum and postpartum periods. J Matern Fetal Med 2000; 9: 173–177.

    PubMed  CAS  Google Scholar 

  11. Ogburn PL Jr, Williams PP, Johnson SB, Holman RT. Serum arachidonic acid levels in normal and preeclamptic pregnancies. Am J Obstet Gynecol 1984; 148: 5–9.

    PubMed  CAS  Google Scholar 

  12. Wang YP, Kay HH, Killam AP. Decreased levels of polyunsaturated fatty acids in preeclampsia. Am J Obstet Gynecol 1991; 164: 1023–1024

    Google Scholar 

  13. Juan H, Sametz W. Dihomo-gamma-hnolenic acid increases the metabolism of eicosapentaenoic acid in perfused vascular tissue. Prostaglandins Leukotrienes Med 1985;19:79–86.

    Article  CAS  Google Scholar 

  14. Das UN. Minerals, trace elements and vitamins interact with essential fatty acids and prostaglandins to prevent hypertension, thrombosis, hypercholesterolemia and atherosclerosis and their attendant complications. IRCS J Med Sci 1985; 13: 684–687.

    CAS  Google Scholar 

  15. Bordet JC, Guichardant M, Lagarde M. Hydroperoxides produced by n-6 lipoxygenation of arachidonic and linoleic acids potentiate synthesis of prostacyclin related compounds. Biochim Biophys Acta 1988; 958: 460–468.

    Article  PubMed  CAS  Google Scholar 

  16. Bordet JC, Guichardant M, Lagarde M. Arachidonic acid strongly stimulates prostaglandin I3 (PGI3) production from eicosapentaenoic acid in human endothelial cells. Biochem Biophys Res Commun 1986; 135:403–410.

    Article  PubMed  CAS  Google Scholar 

  17. Das UN. Hypertension and ascorbic acid. Lancet 2000; 355: 1273.

    Article  PubMed  CAS  Google Scholar 

  18. Qureshi AA, Burger WC, Peterson DM, Elson C. Suppression of cholesterogenesis by plant constituents: review of Wisconsin Contributions to NC-167. Lipids 1985; 20:817–824.

    Article  PubMed  CAS  Google Scholar 

  19. Moore JH, Williams DL. Dietary lmoleic and the accumulation of homo-gamma-linolenic acid in the cholesterol esters of the adrenal gland of the rabbit. Biochim Biophys Acta 1966; 116: 181–183.

    Article  PubMed  CAS  Google Scholar 

  20. Sinclair AJ, Slattery WJ, O’Dea K. The analysis of polyunsaturated fatty acids in meat by gas-liquid chromatography. J Sci Food Agri 1982; 33: 771.

    Article  CAS  Google Scholar 

  21. FAO/WHO. Dietary fats and oils in human nutrition. FAO Food Nutr Paper 1977; No. 3.

    Google Scholar 

  22. McPhail MC, Clayton CC, Snyderman R. A potential second messenger role for unsaturated fatty acids, activation of Ca++ dependent protein kinase. Science 1984; 224,622–625.

    Article  PubMed  CAS  Google Scholar 

  23. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 1984; 308: 693–698.

    Article  PubMed  CAS  Google Scholar 

  24. Berridge MJ, Irvine RF. Inositol triphosphate, a novel second messenger in cellular signal transduction. Nature 1984; 312: 315–321.

    Article  PubMed  CAS  Google Scholar 

  25. Berridge MJ, Irvine RF. Inositol phosphates and cell signalling. Nature 1989; 341: 197–205.

    Article  PubMed  CAS  Google Scholar 

  26. Nishizuka Y. Protein kinase C and lipid signalling for sustained cellular responses. FASEB J 1995; 9: 484–496.

    PubMed  CAS  Google Scholar 

  27. May LG, Johnson S, Krebs S, Newman A, Aronstam RS. Involvement of protein kinase C and protein kinase A in the muscarinic receptor signalling pathways mediating phospholipase C activation, arachidonic acid release and calcium mobilisation. Cell Signal 1999; 11: 179–187.

    Article  PubMed  CAS  Google Scholar 

  28. Chen SG, Murakami K. Effects of cis-fatty acid on protein kinase C activation and protein phosphorylation in the hippocampus. J Pharm Sci Technol 1994; 48: 71–75.

    PubMed  CAS  Google Scholar 

  29. Peters-Golden M, Coburn K, Chauncey JB. Protein kinase C activation modulates arachidonic acid metabolism in cultured alveolar epithelial cells. Exp Lung Res 1992; 18: 535–551

    Article  PubMed  CAS  Google Scholar 

  30. Higaki T, Sawada S, Kono Y, et al. A role of protein kinase C in the regulation of cytosolic phospholipase A(2) in bradykinin-induced PGI(2) synthesis by human vascular endothelial cells. Microvasc Res 1999; 58: 144–155.

    Article  PubMed  CAS  Google Scholar 

  31. Sylvester PW, Birkenfeld HP, Hosick HL, Briski KP. Fatty acid modulation of epidermal growth factor-induced mouse mammary epithelial cell proliferation in vitro. Exp Cell Res 1994; 214: 145–153.

    Article  PubMed  CAS  Google Scholar 

  32. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physiol Rev 1984; 64:1–64.

    PubMed  CAS  Google Scholar 

  33. O’Rahilly S. Uncoupling prtoein2: adiposity angel and diabetes devil? Nature Med 2001;7:770–772.

    Article  PubMed  Google Scholar 

  34. Arsenijevic D, Onuma H, Pecqueur C, et al. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nature Genet 2000; 26: 435–439.

    Article  PubMed  CAS  Google Scholar 

  35. Zhang CY, Baffy G, Perret P, et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 2001; 105: 745–755.

    Article  PubMed  CAS  Google Scholar 

  36. Wang MY, Shimabukuro M, Lee Y, et al. Adeno-virus mediated overexpression of uncoupling protein-2 in pancreatic islets of Zucker diabetic rats increases oxidative activity and improves β-cell function. Diabetes 1999; 48: 1020–1025.

    Article  PubMed  CAS  Google Scholar 

  37. Chan CB, MacDonald PE, Saleh MC, Johns DC, Marban E, Wheeler MB. Overexpression of uncoupling protein 2 inhibits glucose-stimulated insulin secretion from rats islets. Diabetes 1999; 48: 1482–1486.

    Article  PubMed  CAS  Google Scholar 

  38. Esterbauer H, Schneitler C, Oberkofler H, et al. A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Nature Genet 2001; 28: 178–183.

    Article  PubMed  CAS  Google Scholar 

  39. Vidal-Puig A, Grujic D, Zhang C-Y, et al. Energy metabolism in uncoupling protein 3 knock out mice. J Biol Chem 2000; 275: 16258–16266.

    Article  PubMed  CAS  Google Scholar 

  40. Clapham JC, Arch JRS, Chapman H, et al. Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 2000; 406: 415–418.

    Article  PubMed  CAS  Google Scholar 

  41. Cha SH, Fukushima A, Sakuma K, Kagawa Y. Chronic docosahexaenoic acid intake enhances expression of the gene for uncoupling protein 3 and affects pleiotropic mRNA levels in skeletal muscle of aged C57BL/6NJcl mice. J Nutr 2001;131:2636–2642.

    PubMed  CAS  Google Scholar 

  42. Rodriguez VM, Portillo MP, Pico C, Macarulla MT, Palou A. Olive oil feeding up-regultaes uncoupling protein genes in rat brown adipose tissue and skeletal muscle. Am J Clin Nutr 2002; 75: 213–220.

    PubMed  CAS  Google Scholar 

  43. Chevillott E, Rieusset J, Roques M, Desage M, Vidal H. The regulation of uncoupling protein-2 gene expression by ω-6 polyunsaturated fatty acids in human skeletal muscle cells involves multiple pathways, including the nuclear receptor peroxisome proliferator-activated receptor β. J Biol Chem 2001; 276: 10853–10860.

    Article  Google Scholar 

  44. Pedersen SB, Lund S, Buhl ES, Richelsen B. Insulin and contraction directly stimulate UCP2 and UCL3 mRNA expression in rat skeletal muscle in vitro. Biochem Biophys Res Commun 2001; 283: 19–25.

    Article  PubMed  CAS  Google Scholar 

  45. Schrauwen P, Hesselink MKC, Blaak EE, et al. Uncoupling protein 3 content is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 2001; 50: 2870–2873.

    Article  PubMed  CAS  Google Scholar 

  46. Das UN, Kumar KV, Mohan IK. Lipid peroxides and essential fatty acids in patients with diabetes mellitus and diabetic nephropathy. J Nutritional Med 1994; 4: 149–155.

    Article  Google Scholar 

  47. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990; 343: 425–430.

    Article  PubMed  CAS  Google Scholar 

  48. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial Investigators. N Engl J Med 1996; 335: 1001–1009.

    Article  PubMed  CAS  Google Scholar 

  49. Rosendorff C. Statins for prevention of stroke. Lancet 1998; 351: 1002–1003.

    Article  PubMed  CAS  Google Scholar 

  50. Edwards CJ, Hart DJ, Spector TD. Oral statins and increased bone mineral density in postmenopausal women. Lancet 2000; 355: 2218–2219.

    Article  PubMed  CAS  Google Scholar 

  51. Das UN. Essential fatty acids as possible mediators of the actions of statins. Prostaglandins Leukotrienes Eseen Fatty Acids 2001; 65: 37–40.

    Article  CAS  Google Scholar 

  52. Kureishi Y, Luo Z, Shiojima I, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nature Med 2000; 6: 1004–1010.

    Article  PubMed  CAS  Google Scholar 

  53. Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet 1999; 353:983–984.

    Article  PubMed  CAS  Google Scholar 

  54. Strandberg TE, Vanhanen H, Tikkanen MJ. Fffect of statins on C-reactive protein in patients with coronary artery disease. Lancet 1999; 353: 118–119.

    Article  PubMed  CAS  Google Scholar 

  55. Lopez S, Peiretti F, Bonardo B, Juhan-Vague I, Nalbone G. Effect of atorvastatin and fluvastatin on the expression of plasminogen activator inhibitor type-1 in cultured endothelial cells. Atherosclerosis 2000; 152: 359–366.

    Article  PubMed  CAS  Google Scholar 

  56. Romano M, Diomede L, Sironi M, et al. Inhibition of monocyte chemotactic protein-1 synthesis by statins. Lab Invest 2000; 80: 1095–1100.

    Article  PubMed  CAS  Google Scholar 

  57. Rogers MJ. Statins: lower lipids and better bones? Nature Med 2000; 6: 21–23.

    Article  PubMed  CAS  Google Scholar 

  58. Watanabe IM, Umekawa H, Takahashi T, Furuichi Y. Effects of dietary alpha-or gamma-linolenic acid on levels and fatty acid compositions of serum and hepatic lipids, and activity and mRNA abundance of 3-hydroxy-3-methylglutaryl CoA reductase in rats. Comp Biochem Physiol A Mol Integr Physiol 1999; 122: 213–220.

    Article  Google Scholar 

  59. Proksch E, Feingold KR, Elias PM. Epidermal HMG CoA reductase activity in essential fatty acid deficiency: barrier requirements rather than eicosanoid generation regulate cholesterol synthesis. J Invest Dermatol 1992; 99: 216–220. 60.

    Article  PubMed  CAS  Google Scholar 

  60. McVeigh GE, Brennen GM, Johnson GD, et al. Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin dependent) diabetes mellitus. Diabetologia 1993; 36: 33–38.

    Article  Google Scholar 

  61. Lawson DL, Mehta JL, Saldeen K, Mehta P, Saldeen TG. Omega-3 polyunsaturated fatty acids augment endothelium dependent vasorelaxation by enhanced release of EDRF and vasodilator prostaglandins. Eicosanoids 1991; 4: 217–223.

    PubMed  CAS  Google Scholar 

  62. Das UN. Essential fatty acids and osteoporosis. Nutrition 2000; 16: 386–390.

    Article  PubMed  CAS  Google Scholar 

  63. Kumar GS, Das UN. Effect of prostaglandins and their precursors on the proliferation of human lymphocytes and their secretion of tumor necrosis factor and various interleukins. Prostaglandins Leukotrienes Essen Fatty Acids 1994; 50: 331–334.

    Article  CAS  Google Scholar 

  64. Das UN. Beneficial effect of eicosapentaenoic acid and docosahexaenoic acid in the management of systemic lupus erythematosus and its relationship to the cytokine network. Prostaglandins Leukotrienes Essen Fatty Acids 1994; 51: 207–213.

    Article  CAS  Google Scholar 

  65. Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Ann Rev Biochem 1996; 65: 241–269.

    Article  PubMed  CAS  Google Scholar 

  66. Coviella IL, Berse B, Krauss R, Thies RS, Blusztajn JK. Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9. Science 2000; 289: 313–316.

    Article  Google Scholar 

  67. Minami M, Kimura S, Endo T, et al. Dietary docosahexaenoic acid increases cerebral acetylcholine levels and improves passive avoidance performance in stroke-prone spontaneously hypertensive rats. Pharmacol Biochem Behav 1997; 58: 1123–1129.

    Article  PubMed  CAS  Google Scholar 

  68. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet 2000, 356: 1627–1631.

    Article  PubMed  CAS  Google Scholar 

  69. Keely PJ. Rho GTPases as early markers for tumour progression. Lancet 2001; 358: 1744–1745.

    Article  PubMed  CAS  Google Scholar 

  70. Das UN. Essential fatty acids, lipid peroxidation and apoptosis. Prostaglandins Leukotrienes Essen Fatty Acids 1999; 61: 157–163.

    Article  CAS  Google Scholar 

  71. Hobson JP, Rosenfeldt HM, Barak LS, et al. Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science 2001; 291: 1800–1803.

    Article  PubMed  CAS  Google Scholar 

  72. Schmitz PG, Zhang K, Dalai R. Eicosapentaenoic acid suppresses PDGF-induced DNA synthesis in rat mesangial cells: involvement of thromboxane A2. Kidney Int 2000; 57: 1041–1051.

    Article  PubMed  CAS  Google Scholar 

  73. Baumann KH, Hessel F, Larass I, et al. Dietary omega-3, omega-6, and omega-9 unsaturated fatty acids and growth factor and cytokine gene expression in unstimulated and stimulated monocytes. A randomised volunteer study. Arterioscler Thromb Vase Biol 1999; 19: 59–66.

    Article  CAS  Google Scholar 

  74. Pieper AA, Verma A, Zhang J, Snyder SH. Poly (ADP-ribose) polymerase, NO and cell death. Trends Pharmacol Sci 1999; 20: 171–181.

    Article  PubMed  CAS  Google Scholar 

  75. Zingarelli B, Salzman AL, Szabo C. Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circulation Res 1998; 83:85–94.

    Article  PubMed  CAS  Google Scholar 

  76. Soriano FG, Virag L, Jagtap P, et al Endothelial dysfunction: the role of poly (ADP-ribose) polymerase activation. Nature Med 2001; 7: 108–113.

    Article  CAS  Google Scholar 

  77. Burkart V, Wang Z-Q, Radons J, et al. Mice lacking the poly (ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin. Nature Med 1999; 5. 314–319.

    Article  PubMed  CAS  Google Scholar 

  78. Mohan IK, Das UN. Prevention of chemically-induced diabetes mellitus in experimental animals by polyunsaturated fatty acids. Nutrition 2001; 17: 126–151.

    Article  Google Scholar 

  79. Suresh Y, Das UN. Protective action of arachidonic acid against alloxan-induced cytotoxicity and diabetes mellitus. Prostaglandins Leukotrienes Essen Fatty Acids 2001;64:37–52.

    Article  CAS  Google Scholar 

  80. Das UN, Devi GR, Rao KP, Rao MS. Prostaglandins and their precursors can modify genetic damage induced by benzo(a)pyrene and gamma-radiation. Prostaglandins 1985; 29: 911–920.

    Article  PubMed  CAS  Google Scholar 

  81. Das UN, Devi GR, Rao KP, Rao MS. Prostaglandins can modify gamma-radiation and chemical-induced cytotoxicity and genetic damage both in vitro and in vivo. Prostaglandins 1989; 38: 689–716.

    Article  PubMed  CAS  Google Scholar 

  82. Rock KL, Gramm C, Rothstein L, et al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 1994; 78: 761–771.

    Article  PubMed  CAS  Google Scholar 

  83. DiAntonio A, Haghighi AP, Portman SL, Lee JD, Amaranto AM, Goodman CS. Ubiquitination-dependent mechanisms regulate synaptic growth and function. Nature 2001; 412: 449–452.

    Article  PubMed  CAS  Google Scholar 

  84. Shimura H, Schlossmacher MG, Hattori N, et al. Ubiquitination of a new form of α-synclein by parkin from human brain: Implications for Parkinson’s disease. Science 2001;293:263–269.

    Article  PubMed  CAS  Google Scholar 

  85. Xiong X, Chong E, Skach WR. Evidence that endoplasmic reticulum (ER)-associated degradation of cystic fibrosis transmembrane conductance regulator is linked to retrograde translocation from the ER membrane. J Biol Chem 1999; 274: 2616–2624.

    Article  PubMed  CAS  Google Scholar 

  86. Lam YA, Pickart CM, Alban A, et al. Inhibition of the ubiquitin-proteasome system in Alzheimer’s disease. Proc Natl Acad Sci USA 2000; 97: 9902–9906.

    Article  PubMed  CAS  Google Scholar 

  87. Drexler HC, Risau W, Konerding MA. Inhibition of proteasome function induces programmed cell death in proliferating endothelial cells. FASEB J 2000; 14: 65–77.

    PubMed  CAS  Google Scholar 

  88. Rockwell P, Yuan H, Magnusson R, Figueiredo-Pereira ME. Proteasome inhibition of neuronal cells induces proinflammatory response manifested by upregulation of cyclooxygenase-2, its accumulation as ubiquitin conjugates, and production of the prostaglandin PGE (2). Arch Biochem Biophys 2000; 374: 325–333.

    Article  PubMed  CAS  Google Scholar 

  89. Whitehouse AS, Tisdale MJ. Downregulation of ubiquitin-dependent proteolysis by eicosapentaenoic acid in acute starvation. Biochem Biophys Res Commun 2001; 285. 598–602.

    Article  PubMed  CAS  Google Scholar 

  90. Garber K. Taking garbage in, tossing cancer out? Science 2002; 295: 612–613.

    Article  PubMed  CAS  Google Scholar 

  91. Rose DP, Connolly JM. Regulation of tumor angiogenesis by dietary fatty acids and eicosanoids. Nutrition Cancer 2000; 37: 119–127.

    Article  CAS  Google Scholar 

  92. Massaro M, Crluccio MA, Bonfrate C, et al. The double bond in unsaturated fatty acids is the necessary and sufficient requirement for the inhibition of expression of endothelial leukocyte adhesion molecules through interference with nuclear factor-kappa B activation. Lipids 1999; 34 suppl. S213–S214.

    Google Scholar 

  93. Lo CJ, Chiu KC, Fu M, Lo R, Helton S. Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity. J Surg Res 1999;82:216–221

    Article  PubMed  CAS  Google Scholar 

  94. Stuhlmeier KM, Kao JJ, Bach FH. Arachidonic acid influences proinflammatory gene induction by stabilizing the inhibitor-κB α/nuclear factor-κB (NF-κB) complex, thus suppressing the nuclear translocation of NF-κB. J Biol Chem 1997; 272: 24679–24683.

    Article  PubMed  CAS  Google Scholar 

  95. Caygill CP, Charlett A, Hill MJ. Fat, fish, fish oil and cancer. Br J Cancer 1996; 74: 159–164.

    Article  PubMed  CAS  Google Scholar 

  96. Terry P, Lichtenstein P, Feychting M, Ahibom A, Wolk A. Fatty fish consumption and risk of prostate cancer. Lancet 2001; 357. 1764–1766.

    Article  PubMed  CAS  Google Scholar 

  97. Benzaquen LR, Brugnra C, Byers HR, Gattoni-Celli S, Halpenn JA. Clotrimazole inhibits cell proliferation. in vitro and in vivo. Nature Med 1995; 1: 534–540.

    CAS  Google Scholar 

  98. Chow SC, Jondal M. Polyunsaturated free fatty acids stimulate an increase in cytosolic Ca++ by mobilizing the inositol 1,4,5-triphosphate-sensitive Ca++ pool in T cells through a mechanism independent of phosphoinositide turnover. J Biol Chem 1990;265:902–907.

    PubMed  CAS  Google Scholar 

  99. Gamberucci A, Fulceri R, Benedetti A. Inhibition of store-dependent capacitative Ca++ influx by unsaturated fatty acids. Cell Calcium 1997; 21: 375–385.

    Article  PubMed  CAS  Google Scholar 

  100. Palakurthi SS, Fluckiger R, Aktas H, et al. Inhibition of translation initiation mediates the anticancer effect of the n-3 polyunsaturated fatty acid eicosapentaenoic acid. Cancer Res 2000; 60: 2919–2925.

    PubMed  CAS  Google Scholar 

  101. Chen Z-Y, Istfan NW. Docosahexaenoic acid, a major constituent of fish oil diets, prevents activation of cyclin-dependent kinases and S-phase entry by serum stimulation in HT-29 cells. Prostaglandins Leukotrienes Essen Fatty Acids 2001; 64: 67–73.

    Article  CAS  Google Scholar 

  102. Das UN. Tumoricidal action of cis-unsaturated fatty acids and its relationship to free radicals and lipid peroxidation. Cancer Lett 1991; 56: 235–243.

    Article  PubMed  CAS  Google Scholar 

  103. Haider S, Jena N, Croce CM. Inactivation of BCL-2 by phosphorylation. Proc Natl Acad Sci USA 1995; 92: 45–7–4511.

    Google Scholar 

  104. Tyurina YY, Tyurina VA, Certa G, Quinn PJ, Schor NF, Kagan VE. Direct evidence for antioxidant effect of BCL-2 in PC 12 rat phaeochromocytoma cells. Arch Biochem Biophys 1997; 344: 413–423.

    Article  PubMed  CAS  Google Scholar 

  105. Shimabukuro M, Wang MY, Zhou YT, Newgard CB, Unger RH. Protection against lipoapoptosis of beta cells through leptin dependent maintenance of BCL-2 expression. Proc Natl Acad Sci USA 1998; 95: 9558–9561.

    Article  PubMed  CAS  Google Scholar 

  106. Padma M, Das UN. Effect of cis-unsaturated fatty acids on the activity of protein kinases and protein phosphorylation in macrophage tumor (AK-5) cells in vitro. Prostaglandins Leukotrienes Essen Fatty Acids 1999; 60: 55–63.

    Article  CAS  Google Scholar 

  107. Febbraio M, Abumrad NA, Hajjar DP, et al. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem 1999; 274:19055–19062.

    Article  PubMed  CAS  Google Scholar 

  108. Febbraio M, Hajjar DP, Silverstein RL. CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest 2001; 108: 785–791.

    PubMed  CAS  Google Scholar 

  109. Febbraio M, Podrez EA, Smith JD, et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest 2000; 105: 1049–1056.

    Article  PubMed  CAS  Google Scholar 

  110. Miyaoka K, Kuwasako T, Hirano K-I, Nozaki S, Yamashita S, Matsuzawa Y. CD36 deficiency associated with insulin resistance. Lancet 2001; 357: 686–687.

    Article  PubMed  CAS  Google Scholar 

  111. Griffin E, Re A, Hamel N, et al. A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the levels of translation. Nature Med 2001; 7: 840–846.

    Article  PubMed  CAS  Google Scholar 

  112. Spiegelman A. PPARγ in monocytes: less pain, and gain? Cell 1998; 93: 153–155.

    Article  PubMed  CAS  Google Scholar 

  113. Greenwalt DE, Scheck SH, Rhinehart-Jones T. Heart CD36 expression is increased in murine models of diabetes and in mice fed a high fat diet. J Clin Invest 1995; 96: 1382–1388.

    Article  PubMed  CAS  Google Scholar 

  114. Nagy L, Tontonoz P, Alvarez J, Chen H, Evans R. Oxidized LDL regulates macrophage gene expression thrpugh ligand activation of PPARγ. Cell 1998; 93: 229–240.

    Article  PubMed  CAS  Google Scholar 

  115. Tontonoz P, Nagy L, Alvarez J, Thomazy V, Evans R. PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 1998; 93: 241–252.

    Article  PubMed  CAS  Google Scholar 

  116. Pravenec M, Landa V, Zidek V, et al. Transgenic rescue of defective Cd36 ameliorates insulin resistance in spontaneously hypertensive rats. Nature genet 2001; 27: 156–158.

    Article  PubMed  CAS  Google Scholar 

  117. Aitman TJ, Glazier AM, Wallace CA, et al. Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nature genet 1999; 21: 76–83.

    Article  PubMed  CAS  Google Scholar 

  118. Aitman TJ, CD36, insulin resistance, and coronary heart disease. Lancet 2001; 357: 651–652.

    Article  PubMed  CAS  Google Scholar 

  119. Feng J, Han J, Pearce SF, et al. Induction of CD36 expression by oxidized LDL and IL-4 by a common signalling pathway dependent on protein kinase C and PPAR-gamma. J Lipid Res 2000; 41: 688–696.

    PubMed  CAS  Google Scholar 

  120. Spady DK, Kearney DM, Hobbs HH. Polyunsaturated fatty acids up-regulate hepatic scavenger receptor Bl (SR-B1) expression and HDL cholesteryl ester uptake in the hamster. J Lipid Res 1999; 40: 1384–1394.

    PubMed  CAS  Google Scholar 

  121. Das UN. Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus, and coronary heart disease. Prostaglandins Leukotrienes Essen Fatty Acids 1995; 52: 387–391.

    Article  CAS  Google Scholar 

  122. Kumar KV, Das UN. Lipid peroxides and essential fatty acids in patients with coronary heart disease. J Nutritional Med 1994; 4: 33–37.

    Article  Google Scholar 

  123. Das UN. Nutritional factors in the pathobiology of human essential hypertension. Nutrition 2001; 17: 337–346.

    Article  PubMed  CAS  Google Scholar 

  124. Huang Y-J, Fang VS, Chou Y-C, Kwok C-F, Ho L-T. Amelioration of insulin resistance and hypertension in a fructose-fed rat model with fish oil supplementation. Metabolism 1997; 46: 1252–1258.

    Article  PubMed  CAS  Google Scholar 

  125. Mori Y, Murakawa Y, Katoh S, et al. Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima fatty rat,a model of spontaneous non-insulin dependent diabetes mellitus. Metabolism 1997; 46: 1458–1464.

    Article  PubMed  CAS  Google Scholar 

  126. Nobukata H, Ishikawa T, Obata M, Shibutani Y. Long-term administration of highly purified eicosapentaenoic acid ethyl ester prevents diabetes and abnormalities of blood coagulation in male WBN/Kob rats. Metabolism 2000; 49: 912–919.

    Article  PubMed  CAS  Google Scholar 

  127. Ou J, Tu H, Shan B, et al. Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-lc) gene by antagonizing ligand-dependent activation of the LXR. Proc Natl Acad Sci USA 2001; 98: 6027–6032.

    Article  PubMed  CAS  Google Scholar 

  128. Wolfrum C, Borrmann CM, Borchers T, Spener F. Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors α-and γ-mediated gene expression via liver fatty acid binding protein: A signalling path to the nucleus. Proc Natl Acad Sci USA 2001; 98: 2323–2328.

    Article  PubMed  CAS  Google Scholar 

  129. Grand-Perret T, Bouillot A, Perrot A, Commans S, Walker M, Issandou M. SCAP ligands are potent new lipid-lowering drugs. Nature Med 2001; 7: 1332–1338.

    Article  PubMed  CAS  Google Scholar 

  130. de Urquiza AM, Liu S, Sjoberg M, et al. Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 2000; 290: 2140–2144.

    Article  PubMed  Google Scholar 

  131. Mukherjee R, Davies PJ, Crombie DL, et al. Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature 1997; 386: 407–410.

    Article  PubMed  CAS  Google Scholar 

  132. Badwey JA, Curnutte JT, Karnovsky ML. Cis-polyunsaturated fatty acids induce high levels of superoxide production by human neutrophils. J Biol Chem 1981; 256: 12640–12643.

    PubMed  CAS  Google Scholar 

  133. Badwey JA, Curnutte JT, Robinson JM, et al. Effects of free fatty acids on the release of superoxide and on change of shape by human neutrophils. J Biol Chem 1984;259:7870–7877.

    PubMed  CAS  Google Scholar 

  134. Das UN, Padma M, Sangeetha PS, et al. Stimulation of free radical generation in human leukocytes by various stimulants including tumor necrosis factor is a calmodulin dependent process. Biochem Biophys Res Commun 1990; 167: 1030–1036.

    Article  PubMed  CAS  Google Scholar 

  135. Galbraith H, Miller TB, Paton AM, et al. Anti-bacterial activity of long chain fatty acids and the reversal with calcium, magnesium, ergocalciferol and cholesterol. J Appl Bacteriol 1971; 34: 803–813.

    PubMed  CAS  Google Scholar 

  136. Das UN. Antibiotic-like action of essential fatty acids. Canadian Med Assoc J 1985; 132: 1350.

    CAS  Google Scholar 

  137. Kumaratilake LM, Robinson BS, Ferrante A, Poulos A. Antimalarial properties of n-3 and n-6 polyenoic fatty acids: in vitro effects on Plasmodium falciparum and in vivo effects on P. berghei. J Clin Invest 1992; 89: 961–967.

    CAS  Google Scholar 

  138. Das UN, Essential fatty acids as possible enhancers of the beneficial actions of probiotics. Nutrition, in press.

    Google Scholar 

  139. Yang XY, Wang LH, Mihalic K, et al. Interleukm (IL)-4 indirectly suppresses IL-2 production by human T lymphocytes via peroxisome proliferator-activated receptor γ activated by macrophage-derived 12/15-lipoxygenase ligands. J Biol Chem 2002; 277: 3973–3978.

    Article  PubMed  CAS  Google Scholar 

  140. Kumar SG, Das UN. Effect of prostaglandins and their precursors on the proliferation of human lymphocytes and their secretion of tumor necrosis factor and various interleukins. Prostaglandins Leukotrienes Essen Fatty Acids 1994; 50: 331–334.

    Article  CAS  Google Scholar 

  141. Floyd ZE, Stephens JM. Interferon-γ-mediated activation and ubiquitin-proteasome-dependent degradation of PPARγ in adipocytes. J Biol Chem 2002; 277: 40624068.

    Article  CAS  Google Scholar 

  142. Schlager SI, Meltzer MS. Role of macrophage lipids in regulating tumoricidal activity. Cell Immunol 1983; 80:10–19.

    Article  PubMed  CAS  Google Scholar 

  143. Schlager SI, Madden LD, Meltzer MS, et al. Role of macrophage lipids in regulating tumoricidal activity. Cell Immunol 1983; 77: 52–68.

    Article  PubMed  CAS  Google Scholar 

  144. Chandrabose KA, Pottathil R, Borden E, et al. The possible roles of prostaglandin synthetase and cytoplasmic superoxide dismutase in interferon action in homologous cells. In: Powles TJ, Bockman RS, Honn KV, et al., eds. Prostaglandins and Cancer 1 st International Conference New York, Alan R. Liss, Inc., 1982, 345–350.

    Google Scholar 

  145. Seaman WE, Woodcock J. Human and murine natural killer cell activity may require hpoxygenation of arachidonic acid. J Allergy Clin Immunol 1984; 74: 407–411.

    Article  PubMed  CAS  Google Scholar 

  146. Johnson PV. Essential fatty acids, eicosanoids and immunity. Adv Lipid Res 1985; 21: 103.

    Google Scholar 

  147. Das UN. Essential fatty acids in health and disease. J Assoc Physicians India 1999; 47:906–911.

    PubMed  CAS  Google Scholar 

  148. Begin ME, Das UN, Ells G, Horrobin DF. Selective killing of tumor cells by polyunsaturated fatty acids. Prostaglandins Leukotrienes Med 1985; 19:177–186.

    Article  CAS  Google Scholar 

  149. Das UN. Tumoricidal action of cis-unsaturated fatty acids and its relationship to free radicals and lipid peroxidation. Cancer Lett 1991; 56: 235–243.

    Article  PubMed  CAS  Google Scholar 

  150. Sagar PS, Das UN, Koratkar R, Ramesh G, Padma M, Kumar GS. Cytotoxic action of cis-unsaturated fatty acids on human cervical carcinoma (HeLa) cells: Relationship to free radicals, and lipid peroxidation and its modulation by calmodulin antagonists. Cancer Lett 1992; 63: 189–198.

    Article  PubMed  CAS  Google Scholar 

  151. Kumar SG, Das UN. Free radical dependent suppression of mouse myeloma cells by alpha-linolenic and eicosapentaenoic acids in vitro. Cancer Lett 1995; 92: 27–38.

    Article  PubMed  CAS  Google Scholar 

  152. Madhavi N, Das UN. Effect of n-6 and n-3 fatty acids on the survival of vincristine sensitive and resistant human cervical carcinoma cells in vitro. Cancer Lett 1994; 84:31–41.

    Article  PubMed  CAS  Google Scholar 

  153. Das UN, Begin ME, Ells G, Huang YS, Horrobin DF. Polyunsaturated fatty acids augment free radical generation in tumor cells in vitro. Biochem Biophys Res Commun 1987; 145: 15–24.

    Article  PubMed  CAS  Google Scholar 

  154. Das UN, Huang YS, Begin ME, Ells G, Horrobin DF. Uptake and distribution of cis-unsaturated fatty acids and their effect on free radical generation in normal and tumor cells in vitro. Free Rad Biol Med 1987; 3:9–14.

    Article  PubMed  CAS  Google Scholar 

  155. Das UN. Tranforming growth factor-beta: Is it an endogenous cardioprotector? Med Sci Res 1993; 21. 373–375.

    Google Scholar 

  156. Newman MJ. Inhibition of carcinoma and melanoma cell growth by type 1 transforming growth factor β is dependent on the presence of polyunsaturated fatty acids. Proc Natl Acad Sci USA 1990; 87:5543–5547.

    Article  PubMed  CAS  Google Scholar 

  157. Mollerup S, Haugen A. Differential effect of polyunsaturated fatty acids on cell proliferation during human epithelial in vitro carcinogenesis: involvement of epidermal growth factor receptor tyrosine kinase. Br J Cancer 1996; 74: 613–618.

    Article  PubMed  CAS  Google Scholar 

  158. Vacaresse N, Lajoie-Mazenc I, Auge N, et al. Activation of epithelial growth factor receptor pathway by unsaturated fatty acids. Circ Res 1999; 85: 892–899.

    Article  PubMed  CAS  Google Scholar 

  159. Baumann KH, Hessel F, Larass I, et al. Dietary omega-3, pmega-6, and omega-9 unsaturated fatty acids and growth factor and cytokine gene expression in unstimulated and stimulated monocytes. A randomised volunteer study. Arterioscler Thromb Vasc Biol 1999; 19:59–66.

    Article  PubMed  CAS  Google Scholar 

  160. Terano T, Shiina T, Tamura Y. Eicosapentaenoic acid suppressed the proliferation of vascular smooth muscle cells through modulation of various steps of growth signals. Lipids 1996; 31 suppl: S301–S304

    Google Scholar 

  161. Irons CE, Flynn MA, Mok LM, Reynolds EE. Endothelin and PDGF enhance arachidonic acid release and DNA synthesis in vascular smooth muscle cells. Am J Physiol 1996; 270 (6 Pt 1)-C1642–C1646.

    PubMed  CAS  Google Scholar 

  162. Dethlesen SM, Shepro D, D’Amore PA. Arachidonic acid metabolites in bFGF-, PDGF-, and serum-stimulated vascular cell growth. Exp Cell Res 1994; 212: 262–273.

    Article  Google Scholar 

  163. Mizutani M, Okuda Y, Suzuki S, Sawada T, Soma M, Yamashita K. High glucose increases platelet-derived growth factor production in cultured human vascular endothelial cells and preventive effects of eicosapentaenoic acids. Life Sci 1995; 57: PL31–PL35.

    Article  PubMed  CAS  Google Scholar 

  164. Das UN. Hypothesis: can glucose-insulin-potassium regimen in combination with polyunsaturated fatty acids suppress lupus and other inflammatory conditions? Prostaglandins Leukotrienes Essen Fatty Acids 2001; 65: 109–113.

    Article  CAS  Google Scholar 

  165. Zamora R, Alarcon L, Vodovotz Y, et al. Nitric oxide suppresses the expression of Bcl-2 binding protein BNIP3 in hepatocytes. J Biol Chem 2001; 276: 46887–46895.

    Article  PubMed  CAS  Google Scholar 

  166. daCosta CJB, Ogrel AA, McCardy EA, Blanton MP, Baenziger JE. Lipid-protein interactions at the nicotinic acetylcholine receptor: A unique coupling between nicotinic receptors and phosphatidic acid containing lipid bilayers. J Biol Chem 2002; 277: 1249–1254.

    Article  CAS  Google Scholar 

  167. de la Presa Owens S, Innis SM. Docosahexaenoic and arachidonic acid prevent a decrease in dopaminergic and serotoninergic neurotransmitters in frontal cortex caused by a linoleic and α-linolenic acid deficient diet in formula-fed piglets. J Nutr 1999; 129:2088–2093.

    PubMed  Google Scholar 

  168. Nabekura J, Noguchi K, Witt M-R, Nielsen M, Akaike N. Functional modulation of human recombinant γ-aminobutyric acid type A receptor by docosahexaenoic acid. J Biol Chem 1998; 273: 11056–11061.

    Article  PubMed  CAS  Google Scholar 

  169. Wainwright PE, Xing H.-C, Mutsaers L, McCutcheon D, Kyle D. Arachidonic acid offsets the effects on mouse brain and behavior of a diet with a low (n-6): (n-3) ratio and very high levels of docosahexaenoic acid. J Nutr 1997; 127: 184–193.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. EFA Sciences LLC, Norwood, MA, 02062, USA

    Undurti N. Das M.D., FAMS

Authors
  1. Undurti N. Das M.D., FAMS
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Das, U.N. (2002). Long-chain polyunsaturated fatty acids. In: A Perinatal Strategy For Preventing Adult Disease: The Role Of Long-Chain Polyunsaturated Fatty Acids. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8564-4_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-8564-4_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4638-8

  • Online ISBN: 978-1-4419-8564-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation