European Journal of Nutrition

, Volume 46, Issue 2, pp 103–110

Fish oil significantly alters fatty acid profiles in various lipid fractions but not atherogenesis in apo E-KO mice

  • Zuyuan Xu
  • Natalie Riediger
  • Sheila Innis
  • Mohammed H. Moghadasian
ORIGINAL CONTRIBUTION
  • 152 Downloads

Abstract

Background

Consumption of fish oil and n-3 fatty acids is associated with beneficial modifications in plasma lipid levels. The impact of these modifications on development of atherosclerotic lesions merits further investigation.

Aim of the study

The aim of this study was to investigate the impact of fish oil consumption on quality and quantity of lipoprotein fatty acids and its influence on atherosclerosis in apolipoprotein E-knockout (apo E-KO) mice.

Methods

Male apo E-KO mice were treated with 1% dietary fish oil for 14 weeks. Plasma triglycerides (TG), phospholipids, (PL) and cholesteryl ester (CE) fractions were separated using thin layer chromatography. Plasma-free fatty acids (FFA) plus fatty acid contents of TG, PL, CE were determined using gas chromatography. Aortic atherosclerosis was assessed by histological and morphometrical techniques.

Results

Twenty-eight fatty acids were identified in each of the four lipid compartments. High amounts of n-3 fatty acids (eicosapentaenoic (EPA), docosahexaenoic (DHA)) were found in all of these fractions. The levels of EPA and DHA increased by 400 and 150%, respectively, in FFA, TG and PL compartments; higher increases (>500 and 200%) in EPA and DHA were found in CE. This markedly decreased the n-6/n-3 ratios in FFA, TG, PL, and CE by 60, 72, 53, and 61%, respectively. These changes were accompanied by a significant increase in plasma triglyceride levels. Surprisingly, these changes did not affect atherogenesis.

Conclusions

Elevated levels of EPA and DHA do not appear to prevent development of atherosclerotic plaques in this model. Longer studies warrant investigation of the direct benefits of these fatty acids against myocardial damage as clinical consequences of advanced atherosclerosis.

Keywords

apo E-KO mice fish oil fatty acids triglycerides cholesteryl ester phospholipids 

References

  1. 1.
    Hokanson JE, Austin MA (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 3:213–219CrossRefGoogle Scholar
  2. 2.
    Jeppesen J, Hein HO, Suadicani P, Gyntelberg F (1998) Triglyceride concentration and ischemic heart disease: an eight-year follow-up in the Copenhagen Male Study. Circulation 97:1029–1036Google Scholar
  3. 3.
    Chan DC, Watts GF, Mori TA, Barrett PH, Redgrave TG, Beilin LJ (2003) Randomized controlled trial of the effect of n-3 fatty acid supplementation on the metabolism of apolipoprotein B-100 and chylomicron remnants in men with visceral obesity. Am J Clin Nutr 77:300–307Google Scholar
  4. 4.
    Sacks FM, Katan M (2002) Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease. Am J Med 113 Suppl 9B:13S–24SCrossRefGoogle Scholar
  5. 5.
    Ikeda I, Kumamaru J, Nakatani N, Sakono M, Murota I, Imaizumi K (2001) Reduced hepatic triglyceride secretion in rats fed docosahexaenoic acid-rich fish oil suppresses postprandial hypertriglyceridemia. J Nutr 131:1159–1164Google Scholar
  6. 6.
    Lohse P, Brewer HB 3rd, Meng MS, Skarlatos SI, LaRosa JC, Brewer HB Jr (1992) Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene. J Lipid Res 33:1583–1590Google Scholar
  7. 7.
    Moghadasian MH, McManus BM, Nguyen LB, Hill J, Scudamore C, Frohlich JJ (2001) Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans. FASEB J 15:2623–2630CrossRefGoogle Scholar
  8. 8.
    Lomnitski L, Oron L, Sklan D, Michaelson DM (1999) Distinct alterations in phospholipid metabolism in brains of apolipoprotein E-deficient mice. J Neurosci Res 58:586–592CrossRefGoogle Scholar
  9. 9.
    Zhang SH, Reddick RL, Piedrahita JA, Maeda N (1992) Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258:468–4671CrossRefGoogle Scholar
  10. 10.
    Moghadasian MH, McManus BM, Godin DV, Rodrigues B, Frohlich JJ (1999) Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice: possible mechanisms of action. Circulation 99:1733–1739Google Scholar
  11. 11.
    Moghadasian MH, McManus BM, Pritchard PH, Frohlich JJ (1997) “Tall oil”-derived phytosterols reduce atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 17:119–126Google Scholar
  12. 12.
    Davis HR Jr, Compton DS, Hoos L, Tetzloff G (2001) Ezetimibe, a potent cholesterol absorption inhibitor, inhibits the development of atherosclerosis in ApoE knockout mice. Arterioscler Thromb Vasc Biol 21:2032–2038Google Scholar
  13. 13.
    Hino A, Adachi H, Toyomasu K, Yoshida N, Enomoto M, Hiratsuka A, Hirai Y, Satoh A, Imaizumi T (2004) Very long chain n-3 fatty acids intake and carotid atherosclerosis: an epidemiological study evaluated by ultrasonography. Atherosclerosis 176:145–149CrossRefGoogle Scholar
  14. 14.
    Kris-Etherton PM, Taylor DS, Yu-Poth S, Huth P, Moriarty K, Fishell V, Hargrove RL, Zhao G, Etherton TD (2000) Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 71(1 Suppl):179S–188SGoogle Scholar
  15. 15.
    Kris-Etherton PM, Harris WS, Appel LJ, AHA Nutrition Committee, American Heart Association (2003) Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol 23:151–152CrossRefGoogle Scholar
  16. 16.
    Innis SM, Dyer RA (1999) Dietary canola oil alters hematological indices and blood lipids in neonatal piglets fed formula. J Nutr 129:1261–1268Google Scholar
  17. 17.
    Stone NJ (1996) Fish consumption, fish oil, lipids, and coronary heart disease. Circulation 94:2337–2340Google Scholar
  18. 18.
    Zhang J, Sasaki S, Amano K, Kesteloot H (1999) Fish consumption and mortality from all causes, ischemic heart disease, and stroke: an ecological study. Prev Med 28:520–529CrossRefGoogle Scholar
  19. 19.
    Mizushima S, Moriguchi EH, Ishikawa P, Hekman P, Nara Y, Mimura G, Moriguchi Y, Yamori Y (1997) Fish intake and cardiovascular risk among middle-aged Japanese in Japan and Brazil. J Cardiovasc Risk 4:191–199CrossRefGoogle Scholar
  20. 20.
    Hu FB, Bronner L, Willett WC, Stampfer MJ, Rexrode KM, Albert CM, Hunter D, Manson JE (2002) Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA 287:1815–1821CrossRefGoogle Scholar
  21. 21.
    von Schacky C (1987) Prophylaxis of atherosclerosis with marine omega-3 fatty acids. A comprehensive strategy. Ann Intern Med 107:890–899Google Scholar
  22. 22.
    Dolecek TA (1992) Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial. Proc Soc Exp Biol Med 200:177–182Google Scholar
  23. 23.
    Ascherio A, Rimm EB, Stampfer MJ, Giovannucci EL, Willett WC (1995) Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 332:977–982CrossRefGoogle Scholar
  24. 24.
    Albert CM, Hennekens CH, O’Donnell CJ, Ajani UA, Carey VJ, Willett WC, Ruskin JN, Manson JE (1998) Fish consumption and risk of sudden cardiac death. JAMA 279:23–28CrossRefGoogle Scholar
  25. 25.
    Guallar E, Aro A, Jimenez FJ, Martin-Moreno JM, Salminen I, van’t Veer P, Kardinaal AF, Gomez-Aracena J, Martin BC, Kohlmeier L, Kark JD, Mazaev VP, Ringstad J, Guillen J, Riemersma RA, Huttunen JK, Thamm M, Kok FJ (1999) Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study. Arterioscler Thromb Vasc Biol 19:1111–1118Google Scholar
  26. 26.
    Kromhout D, Feskens EJ, Bowles CH (1995) The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. Int J Epidemiol 24:340–345CrossRefGoogle Scholar
  27. 27.
    Ebbesson SO, Risica PM, Ebbesson LO, Kennish JM (2005) Eskimos have CHD despite high consumption of omega-3 fatty acids: the Alaska Siberia project. Int J Circumpolar Health 64:387–395Google Scholar
  28. 28.
    Ebbesson SO, Risica PM, Ebbesson LO, Kennish JM, Tejero ME (2005) Omega-3 fatty acids improve glucose tolerance and components of the metabolic syndrome in Alaskan Eskimos: the Alaska Siberia project. Int J Circumpolar Health 64:396–408Google Scholar
  29. 29.
    Harris WS, Sands SA, Windsor SL, Ali HA, Stevens TL, Magalski A, Porter CB, Borkon AM (2004) Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with erythrocytes and response to supplementation. Circulation 110:1645–1649CrossRefGoogle Scholar
  30. 30.
    Harris WS, Von Schacky C (2004) The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med 39:212–220CrossRefGoogle Scholar
  31. 31.
    Harris WS (1989) Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review. J Lipid Res 30:785–807Google Scholar
  32. 32.
    Silverman DI, Reis GJ, Sacks FM, Boucher TM, Pasternak RC (1990) Usefulness of plasma phospholipid n-3 fatty acid levels in predicting dietary fish intake in patients with coronary artery disease. Am J Cardiol 66:860–862CrossRefGoogle Scholar
  33. 33.
    Leaf A, Kang JX, Xiao YF, Billman GE (2003) Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation 107:2646–2652CrossRefGoogle Scholar
  34. 34.
    Culp BR, Lands WE, Lucches BR, Pitt B, Romson J (1980) The effect of dietary supplementation of fish oil on experimental myocardial infarction. Prostaglandins 20:1021–1031CrossRefGoogle Scholar
  35. 35.
    McLennan PL, Bridle TM, Abeywardena MY, Charnock JS (1993) Comparative efficacy of n-3 and n-6 polyunsaturated fatty acids in modulating ventricular fibrillation threshold in marmoset monkeys. Am J Clin Nutr 58:666–669Google Scholar
  36. 36.
    McLennan PL (1993) Relative effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on cardiac arrhythmias in rats. Am J Clin Nutr 57:207–212Google Scholar
  37. 37.
    McLennan PL, Abeywardena MY, Charnock JS (1988) Dietary fish oil prevents ventricular fibrillation following coronary artery occlusion and reperfusion. Am Heart J 116:709–717CrossRefGoogle Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2007

Authors and Affiliations

  • Zuyuan Xu
    • 1
    • 2
  • Natalie Riediger
    • 1
    • 2
  • Sheila Innis
    • 3
  • Mohammed H. Moghadasian
    • 1
    • 2
    • 4
  1. 1.Dept. of Human Nutritional SciencesUniversity of ManitobaWinnipegCanada
  2. 2.Canadian Centre for Agri-food Research in Health and MedicineSt. Boniface Hospital Research CentreWinnipegCanada
  3. 3.Dept. of PeadiatricsUniversity of British ColumbiaVancouverCanada
  4. 4.WinnipegCanada

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