The Absorbability of Free and Esterified Eicosapentaenoic Acid

Its Lipoprotein Transport and Clearance
  • Isabel S. Chen
  • Satchithanandam Subramanian
  • Marie M. Cassidy
  • George V. Vahouny
  • Alan J. Sheppard
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Although the antithrombotic and hypolipidemic effects of certain fish oils containing -3 fatty acids are extensively documented, little is known regarding the digestibility, absorption, lipoprotein transport, and chylomicron clearance of lipids containing these acids. Systematic studies have now been conducted to demonstrate the following: the rate and extent of absorption of unesterified eicosapentaenoic acid (EPA) into thoracic duct lymph of rats are comparable to that of oleic and arachidonic acids; the same is true with respect to recovery of eicosapentaenoic, oleic, and arachidonic acids as chylomicron triglycerides. However, based on lymphatic recoveries of salmon oil fatty acids, the digestibility of triglycerides containing EPA is significantly less efficient than for corn oil, which is enriched in oleic and linoleic acids. In order to determine aspects of lipoprotein triglyceride clearance, mesenteric lymph chylomicrons, enriched in eicosapentaenoic or oleic acids, were prepared. In order to assess the activity of peripheral lipoprotein lipase (LPL) on these chylomicrons, the nonworking rat heart model was used for recirculating perfusion. With this membrane-supported LPL system, clearance rates of chylomicron triglycerides enriched with either EPA or oleic acid were identical. Furthermore, oxidation of the extracted fatty acids and incorporation into mycocardial esterified lipids, with the exception of phospholipid, were comparable for the two fatty acids. Finally, overall clearance rates of chylomicron triglycerides enriched with EPA or oleic acid were compared following intravenous injection into rats. Although initial clearances rates (2–10 min) were comparable for chylomicrons containing either fatty acid, the clearance of EPA-enriched chylomicrons was significantly slower at 25–90 min (P < 0.05). Nevertheless, at each time point, the distributions of the remaining oleate and EPA among circulating lipoproteins were comparable. These studies suggest that except for less efficient intestinal digestibility of EPA-containing fish oils, the subsequent absorption, transport, and clearance of EPA in the rat are typical of other more common fatty acids.


Oleic Acid Arachidonic Acid Eicosapentaenoic Acid Lipid Emulsion Sodium Taurocholate 
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  1. Ahrens, E. H., Hirsch, J., Peterson, M. L., Insull, W., Stoffel, W., and Farquhar, J. W., 1959, The effect of human serum-lipid of a dietary fat, highly unsaturated, but poor in essential fatty acids, Lancet 1:115–119.PubMedCrossRefGoogle Scholar
  2. Bang, H. O., and Dyerberg, J., 1972, Plasma lipids and lipoproteins in Greenland Eskimos, Acta Med. Scand. 192:84–94.Google Scholar
  3. Bang, H. O., and Dyerberg, J., 1980, Lipid metabolism and ischemic heart disease, in: Advanced Nutrition Research ,Vol. 3 (H. H. Draper, ed.), Plenum Press, New York, pp. 1–22.Google Scholar
  4. Bang, H. O., and Dyerberg, J., 1981, Personal reflections of the incidence of ischemic heart disease in Oslo during the Second World War, Acta Med. Scand. 210:245–248.PubMedCrossRefGoogle Scholar
  5. Bang, H. O., Dyerberg, J., and Hjorne, N., 1976, The composition of food consumed by Greenland Eskimos, Acta Med. Scand. 100:69–73.Google Scholar
  6. Bottino, N. R., Vandenberg, G. A., and Reiser, R., 1967, Resistance of certain long-chain polyunsaturated fatty acids of marine oils to pancreatic lipase hydrolysis, Lipids 2:489–493.PubMedCrossRefGoogle Scholar
  7. Brockerhoff, H., Hoyle, R. J., and Huang, P. C., 1966, Positional distribution of fatty acids of a polar bear and a seal, Can. J. Biochem. 44:1519–1525.CrossRefGoogle Scholar
  8. Culp, B. R., Titus, B. G., and Lands, W. E. M., 1979, Inhibition of prostaglandin synthesis by eicosapentaenoic acid, Prostaglandins Med.3:369–378.CrossRefGoogle Scholar
  9. Folch, J., Lees, M., and Sloane Stanley, G. H., 1957, A simple method for the isolation and purification of total lipid from animal tissue, J. Biol. Chem. 226:497–509.PubMedGoogle Scholar
  10. Gartner, S.Vahouny, G. V1972.Effects of epinephrine and cAMP on perfused rat hearts, Am. J. Physiol222:1121,1124.PubMedGoogle Scholar
  11. Garton, G. A., Hilyditch, T. P., and Meara, M. L., 1952, The composition of depot fat of a pig fed on a diet rich in whale oil, Biochem. J. 50:617–524.Google Scholar
  12. Goodnight, S. H., Jr., Harris, W. S., and Connor, W. E., 1981, The effect of dietary -3 fatty acids on platelet composition and function in man: A prospective, controlled study. Blood 58:880–884.Google Scholar
  13. Goodnight, S. H., Jr., Harris, W. S., Connor, W. E., and Illingworth, D. E., 1982, Polyunsaturated fatty acids, hyperlipidemia and thrombosis, Arteriosclerosis 2:87–113.PubMedCrossRefGoogle Scholar
  14. Harris, W. S., Connor, W. E., and Goodnight, S. H., Jr., 1982, Dietary fish oils, plasma lipids and platelets in man, in: Essential Fatty Acids and Prostaglandins (R. T. Holman, ed.), Pergamon Press, Oxford, pp. 75–79.Google Scholar
  15. Harris, W. S., Connor, W. E., Inkeles, S. G., and Illingworth, D. R., 1984, Dietary omega-3 fatty acids prevent carbohydrate-induced hypertriglyceridemia, Metabolism 33:1016–1019.PubMedCrossRefGoogle Scholar
  16. Havel, R. J., Eder, H. A., and Bragdon, J. H., 1955, The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum, J. Clin. Invest. 34:1345–1353.PubMedCrossRefGoogle Scholar
  17. Hay, C. R. M., Durber, A. P., and Saynor, R., 1982, Effect of fish oil on platelet kinetics in patients with ischaemic heart disease, Lancet 2:1269–1272.CrossRefGoogle Scholar
  18. Hirai, A., Hamazaki, T., Terano, T., Nishikawa, T., Tamura, Y., Kumagai, A., and Sajiki, J., 1980, Eicosapentaenoic acid and platelet function in Japanese, Lancet 2:1132–1133.PubMedCrossRefGoogle Scholar
  19. Illingworth, D. R., Harris, W. S. and Connor, W. E., 1984, Inhibition of low density lipoprotein synthesis by dietary omega-3 fatty acids in humans, Arteriosclerosis 4:270–275.PubMedCrossRefGoogle Scholar
  20. Jakobowski, J. A., and Ardlie, N. G., 1980, Cyclic AMP-independent inhibition of human platelet function by eicosapentaenoic acid, Thromb. Res. 17:751–752.CrossRefGoogle Scholar
  21. Kromhont, D., Bosschieter, E. B., and Coulander, C. L., 1985, The inverse relation between fish consumption and 20-year mortality from coronary heart disease, N. Engl. J. Med. 312(19): 1205-1209.CrossRefGoogle Scholar
  22. Needleman, P., and Sprecher, H., 1979, Mechanism underlying the inhibition of platelet aggregation by eicosapentaenoic acid and its metabolites, Adv. Prostaglandin Thromboxane Res. 6:61–68.Google Scholar
  23. Needleman, P., Raz, A., Minkes, M. S., Ferrendelli, J. A., and Sprecher, H., 1979, Triene prostaglandins: Prostacyclin and thromboxane biosynthesis and unique biological properties, Proc. Natl. Acad. Sci. U.S.A. 76:944–948.CrossRefGoogle Scholar
  24. Needleman, P., Whitaker, M. C., and Sprecher, H., 1980, Manipulation of platelet aggregation by prostaglandins and their fatty acid precursors-pharmacological basis for a therapeutic approach, Prostaglandins 19:165–181.CrossRefGoogle Scholar
  25. Peifer, J. J., Jansen, F., Ahn, P., Cox, W., and Lunberg, W. O., 1960, Studies on the distribution of lipids in hypercholesterolemic rats. 1. The effect of feeding palmitate, oleate, linoleate, linolenate, menhaden, and tuna oil, Arch. Biochem. Biophys. 86:302–308.PubMedCrossRefGoogle Scholar
  26. Peifer, J. J., Lunberg, W. O., Ishio, S., and Warmanen, E., 1965, Studies of the distribution of lipids in hypercholesterolemic rats. 3. Changes in hypercholesterolemia and tissue fatty acids induced by dietary fats and marine oil fractions, Arch. Biochem. Biophys. 110:270–283.PubMedCrossRefGoogle Scholar
  27. Ross, R., and Glomset, J. A., 1976a, The pathogenesis of atherosclerosis (First of two parts), N. Engl. J. Med. 285(7):369–377.CrossRefGoogle Scholar
  28. Ross, R., and Glomset, J. A., 1976b, The pathogenesis of atherosclerosis (Second of two parts), N. Engl. J. Med. 285(8):429–435.Google Scholar
  29. Spector, A. A., Kaduce, T. L., Figard, P. H., Norton, K. C., Hoak, J. C. and Czervionke, R. L., 1983, Eicosapentaenoic acid and prostacyclin production by cultured human endothelial cells, J. Lipid Res. 24:1595–1604.PubMedGoogle Scholar
  30. Treadwell, C. R., and Vahouny, G. V., 1968, Cholesterol absorption, in: Handbook of Physiology: Alimentrary Canal ,Sec. 6, Vol. II, American Physiology Society, Washington, pp. 1407–1438.Google Scholar
  31. Vahouny, G. V., Katzen, R., and Entenman, C 1966, Glucose uptake by isolated perfused hearts from fed and fasted rats, Proc. Soc. Exp. Biol. Med. 121:923.PubMedGoogle Scholar
  32. Vahouny, G. V. Blendermann, E. M., Gallo, L. L., and Treadwell, C. R., 1980a, Differential transport of cholesterol and oleic acid in lymph, J. Lipid Res. 21:415–424.PubMedGoogle Scholar
  33. Vahouny, G. V., Roy, T., Gallo, L. L., Story, J. A., Kritchevsky, D., and Cassidy, M. M., 1980b, Dietary fiber. III. Effects of chronic intake on cholesterol absorption and metabolism in the rat, Am. J. Clin. Nutr. 33:2182–2191.PubMedGoogle Scholar
  34. Witaker, M. O., Wyche, A., Fitzpatrick, F., Sprecher, H., and Needleman, P., 1979, Triene prostaglandins: Prostaglandin D3 and eicosapentaenoic acid as potential antithrombotic substances, Proc. Natl. Acad. Sci. U.S.A. 76:5919–5923.CrossRefGoogle Scholar
  35. Wong, S. H., Nestel, P. J., Trimble, R. P., Stoner, G. B., Illman, R. J., and Topping, D. L., 1984, The adaptive effects of dietary fish and safflower oil on lipid and lipoprotein metabolism in perfused rat liver, Biochim. Biphys. Acta 792(2): 103–109.Google Scholar
  36. Yotakis, L. D. O., 1981, The preventive effects of polyunsaturated fats on thrombosis, Thromb. Haemostas. 46:65–68.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Isabel S. Chen
    • 1
  • Satchithanandam Subramanian
    • 1
  • Marie M. Cassidy
    • 1
  • George V. Vahouny
    • 1
  • Alan J. Sheppard
    • 2
  1. 1.Departments of Biochemistry and Physiologythe George Washington University School of Medicine and Health SciencesUSA
  2. 2.Division of NutritionFood and Drug AdministrationUSA

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