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The ratio of n-6 to n-3 polyunsaturated fatty acids in the rat diet alters serum lipid levels and lymphocyte functions

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Lipids

Abstract

Previous studies have reported that feeding rats diets rich in fish oils, which contain high proportions of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic and docosahexaenoic acids, results in lowering of blood lipid levels and suppression of lymphocyte functions testedex vivo andin vivo. The effects of other n-3 PUFA, such as α-linolenic acid, which is found in high proportions in linseed oil, are not as well documented. Therefore, in the present study, weanling male rats were fed for six weeks on one of five high-fat (20% by weight) diets made by mixing together sunflower and linseed oils; the resulting blends had n-6/n-3 PUFA ratios of 112.5:1 (pure sunflower oil), 14.8:1, 6.5:1, 0.8:1, and 0.33:1 (pure linseed oil); the levels of all other components in the diet were identical. The final body weight and total dissectable fat were lowest in rats fed the pure linseed oil diet. Serum cholesterol, triacylglycerol and nonesterified fatty acid concentrations decreased as the n-6/n-3 PUFA ratio of the diet decreased. The fatty acid composition of the serum and of spleen lymphocytes was influenced by the diet fed-there was a progressive decrease in the proportions of linoleic and arachidonic acids and a progressive increase in the proportion of α-linolenic acid as the n-6/n-3 PUFA ratio of the diet decreased. Eicosapentaenoic and docosahexaenoic acids were detected in the serum but not in spleen lymphocytes. Inclusion of α-linolenic acid in the diet resulted in significant suppression of spleen lymphocyte proliferation in response to the T-cell mitogen concanavalin A and in spleen lymphocyte natural killer cell activity, both measuredex vivo. The localized graft vs. host response, a measure of cellmediated immunityin vivo, progressively decreased as the n-6/n-3 PUFA ratio of the diet decreased. Thus, this study shows that dietary α-linolenic acid results in lowered blood lipid levels and suppressed lymphocyte functionsex vivo andin vivo. With respect to these effects, α-linolenic acid is as potent as dietary fish oil.

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Abbreviations

CHD:

coronary heart disease

Con A:

concanavalin A

LDH:

lactate dehydrogenase

LT:

leukotriene

NEFA:

nonesterified fatty acid

NK:

natural killer

PBS:

phosphate-buffered saline

PLN:

popliteal lymph node

PUFA:

polyunsaturated fatty acids

TAG:

triacylglycerol

References

  1. Keys, A. (1970) Coronary Heart Disease in Seven Countries,Circulation, 41, 1–211.

    Google Scholar 

  2. Harris, W.S. (1989) Fish Oils and Plasma Lipid and Lipoprotein Metabolism in Humans: A Critical Review,J. Lipid Res., 30, 785–807.

    PubMed  CAS  Google Scholar 

  3. Dolphin, P.J., Amy, R.M., Koeslag, D.G., Limoges, B.F., and Russell, J.C. (1988) Reduction in Hyperlipidemia in the LA/N Corpulent Rat by Dietary Fish Oil Containing n-3 Fatty Acids,Biochim. Biophys. Acta 962, 317–329.

    PubMed  CAS  Google Scholar 

  4. Garg, M.L., Wierzbicki, A.A., Thomson, A.B.R., and Clandinin, M.T. (1988) Fish Oil Reduces Cholesterol and Arachidonic Acid Content More Efficiently in Rats Fed Diets Containing Low Linoleic to Saturated Fatty Acid Ratios,Biochim. Biophys. Acta, 962, 337–344.

    PubMed  CAS  Google Scholar 

  5. de Schrijver, R., Vermeulen, D., and Viane, E. (1991) Lipid Metabolism Responses in Rats Fed Beef Tallow, Native or Randomised Fish Oil and Native or Randomised Peanut Oil,J. Nutr. 121, 948–955.

    PubMed  Google Scholar 

  6. Hostmark, A.T., Lystad, E., Huag, A., and Eilersten, E. (1989) Plasma Lipids, Lipoproteins and Fecal Excretion of Neutral Sterols and Bile Acids in Rats Fed Various High Fat Diets or a Low Fat/High Sucrose Diet,J. Nutr., 119, 356–363.

    PubMed  CAS  Google Scholar 

  7. Al-Shirbaji, A., Larsson-Backstrom, C., Berglund, L., Eggertsen, G., and Bjorkhem, I. (1991) Effect of n-3 Fatty Acids on the Key Enzymes Involved in Cholesterol and Triglyceride Turnover in Rat Liver,Lipids, 26, 385–389.

    Google Scholar 

  8. Yaqoob, P., Sherrington, E.J., Jeffery, N.M., Sanderson, P., Harvey, D.J., Newsholme, E.A., and Calder, P.C. (1995) Comparison of the Effects of a Range of Dietary Lipids Upon Serum and Tissue Lipid Composition in the Rat.Int. J. Biochem. Cell Biol. 27, 297–310.

    Article  PubMed  CAS  Google Scholar 

  9. Dyerberg, J., Mortensen, J.Z., Nielsen, A.H., and Schmidt, E.B. (1982) n-3 Polyunsaturated Fatty Acids and Ischaemic Heart Disease,Lancet, 2, 614.

    Article  CAS  Google Scholar 

  10. Ulbricht, T.L.V., and Southgate, D.A.T. (1991) Coronary Heart Disease: Seven Dietary Factors,Lancet, 338, 985–992.

    Article  PubMed  CAS  Google Scholar 

  11. Kromhout, D., Bosschieter, E.B., and de Lezenne Coulander, C. (1985) The Inverse Relation Between Fish Consumption and 20-Year Mortality from Coronary Heart Disease,New. Engl. J. Med. 312, 1205–1206.

    Article  PubMed  CAS  Google Scholar 

  12. Kromann, N., and Green, A. (1980) Epidemiological Studies in the Upernavik District, Greenland,Acta Med. Scand. 208, 401–406.

    Article  PubMed  CAS  Google Scholar 

  13. Yaqoob, P., Newsholme, E.A., and Calder, P.C. (1994) The Effect of Dietary Lipid Manipulation on Rat Lymphocyte Subsets and Proliferation,Immunology 82, 603–610.

    PubMed  CAS  Google Scholar 

  14. Calder, P.C., Bond, J.A., Bevan, S.J., Hunt, S.V., and Newsholme, E.A. (1991) Effect of Fatty Acids on the Proliferation of Concanavalin A-Stimulated Rat Lymph Node Lymphocytes,Int. J. Biochem. 23, 579–588.

    Article  PubMed  CAS  Google Scholar 

  15. Calder, P.C., Bevan, S.J., and Newsholme, E.A. (1992) The Inhibition of T-Lymphocyte Proliferation by Fatty Acids Isvia an Eicosanoid-Independent Mechanism,Immunology 75, 108–115.

    PubMed  CAS  Google Scholar 

  16. Calder, P.C., Yaqoob, P., and Newsholme, E.A. (1994) Triacylglycerol Metabolism by Lymphocytes and the Effect of Triacylglycerols upon Lymphocyte Proliferation,Biochem. J. 298, 605–611.

    PubMed  CAS  Google Scholar 

  17. Calder, P.C., and Newsholme, E.A. (1992) Unsaturated Fatty Acids Suppress Interleukin-2 Production and Transferrin Receptor Expression by Concanavalin A-Stimulated Rat Lymphocytes,Mediat. Inflamm. 1, 107–115.

    CAS  Google Scholar 

  18. Calder, P.C., and Newsholme, E.A. (1992) Polyunsaturated Fatty Acids Suppress Human Peripheral Blood Lymphocyte Proliferation and Interleukin-2 Production,Clin. Sci. 82, 695–700.

    PubMed  CAS  Google Scholar 

  19. Calder, P.C., and Newsholme, E.A. (1993) Influence of Antioxidant Vitamins on Fatty Acid Inhibition of Lymphocyte Proliferation,Biochem. Mol. Biol. Int. 29, 175–183.

    PubMed  CAS  Google Scholar 

  20. Kumar, G.S., Das, U.N., Kumar, K.V., Madhavi, N., Das, N.P., and Tan, B.K.H. (1992) Effect of n-6 and n-3 Fatty Acids on the Proliferation of Human Lymphocytes and Their Secretion of TNF-α and IL-2in vitro, Nutr. Res. 12, 815–823.

    Article  CAS  Google Scholar 

  21. Soyland, E., Nenseter, M.S., Braathen, L., and Drevon, C.A. (1993) Very Long Chain n-3 and n-6 Polyunsaturated Fatty Acids Inhibit Proliferation of Human T-Lymphocytesin vitro, Eur. J. Clin. Invest. 23, 112–121.

    PubMed  CAS  Google Scholar 

  22. Yamashita, N., Maruyama, M., Yamazaki, K., Hamazaki, T., and Yano, S. (1991) Effect of Eicosapentaenoic and Docosahexaenoic Acid on Natural Killer Cell Activity in Human Peripheral Blood Lymphocytes,Clin. Immunol. Immunopath. 59, 335–345.

    Article  CAS  Google Scholar 

  23. Fujikawa, M., Yamashita, N., Yamazaki, K., Sugiyama, E., Suzuki, H., and Hamazaki, T. (1992) Eicosapentaenoic Acid Inhibits Antigen-Presenting Cell Function of Murine Splenocytes,Immunology 75, 330–335.

    PubMed  CAS  Google Scholar 

  24. Marshall, L.A., and Johnston, P.V. (1985) The Influence of Dietary Essential Fatty Acids on Rat Immunocompetent Cell Prostaglandin Synthesis and Mitogen-induced Blastogenesis,J. Nutr. 115, 1572–1580.

    PubMed  CAS  Google Scholar 

  25. Kelley, D.S., Nelson, G.J., Serrato, C.M., Schmidt, P.C., and Branch, L.B. (1988) Effects of Type of Dietary Fat on Indices of Immune Status of Rabbits,J. Nutr. 118, 1376–1384.

    PubMed  CAS  Google Scholar 

  26. Fritsche, K.L., Cassity, N.A., and Huang, S.-C. (1991) Effect of Dietary Fat Source on Antibody Production and Lymphocyte Proliferation in Chickens,Poultry Sci. 70, 611–617.

    CAS  Google Scholar 

  27. Calder, P.C., Costa-Rosa, L.F.B.P., and Curi, R. (1995) Effects of Feeding Lipids of Different Fatty Acid Compositions upon Rat Lymphocyte Proliferation,Life Sci. 56, 455–463.

    Article  PubMed  CAS  Google Scholar 

  28. Yaqoob, M., and Calder, P.C. (1995) The Effects of Dietary Lipid Manipulation on the Production of Murine T-Cell-Derived Cytokines,Cytokine 7, 548–553.

    Article  PubMed  CAS  Google Scholar 

  29. Sanderson, P., Yaqoob, P., and Calder, P.C. (1995) Effects of Dietary Lipid Manipulation upon Rat Spleen Lymphocyte Functions and the Expression of Lymphocyte Surface Molecules,J. Nutr. Environ. Med. 5, 119–132.

    CAS  Google Scholar 

  30. Yaqoob, P., Newsholme, E.A., and Calder, P.C. (1995) The Effect of Dietary Lipids on Leucocyte Subsets and Proliferation in Rat Whole Blood,Nutr. Res. 15, 279–287.

    Article  CAS  Google Scholar 

  31. Calder, P.C. (1995) Fatty Acids, Dietary Lipids and Lymphocyte Functions,Biochem. Soc. Trans. 23, 302–309.

    PubMed  CAS  Google Scholar 

  32. Calder, P.C. (1996) Effects of Fatty Acids and Dietary Lipids on Cells on the Immune System,Proc. Nutr. Soc. 55, 127–150.

    PubMed  CAS  Google Scholar 

  33. Olson, L.M., Clinton, S.K., Everitt, J.I., Johnston, P.V., and Visek, W.J. (1987) Lymphocyte Activation, Cell-Mediated Cytotoxicity and Their Relationship to Dietary Fat-Enhanced Mammary Tumorigenesis in C3H/OUJ Mice,J. Nutr. 117, 955–963.

    PubMed  CAS  Google Scholar 

  34. Erickson, K.L. (1984) Dietary Fat Influences on Murine Melanoma Growth and Lymphocyte-Mediated Cytotoxicity,J. Natl. Cancer Inst. 72, 115–120.

    PubMed  CAS  Google Scholar 

  35. Fritsche, K.L., and Johnston, P.V. (1989) Modulation of Eicosanoid Production and Cell-Mediated Cytotoxicity by Dietary α-Linolenic Acid in BALB/c Mice,Lipids 24, 305–311.

    PubMed  CAS  Google Scholar 

  36. Fritsche, K.L., and Johnstone, P.V. (1990) Effect of Dietary Omega-3 Fatty Acids on Cell-Mediated Cytotoxicity in BALB/c Mice,Nutr. Res. 10, 577–588.

    Article  CAS  Google Scholar 

  37. Fritsche, K.L., and Cassity, N.A. (1992) Dietary n-3 Fatty Acids Reduce Antibody-Dependent Cell Cytotoxicity and Alter Eicosanoid Release by Chicken Immune Cells,Poultry Sci. 71, 1646–1657.

    CAS  Google Scholar 

  38. Meydani, S.N., Yogeeswaran, G., Liu, S., Baskar, S., and Meydani, M. (1988) Fish Oil and Tocopherol-Induced Changes in Natural Killer Cell-Mediated Cytotoxicity and PGE2 Synthesis in Young and Old Mice,J. Nutr. 118, 1245–1252.

    PubMed  CAS  Google Scholar 

  39. Berger, A., German, J.B., Chiang, B.L., Ansari, A.A., Keen, C.L., Fletcher, M.P., and Gershwin, M.R. (1993) Influence of Feeding Unsaturated Fats on Growth and Immune Status of Mice,J. Nutr. 123, 225–233.

    PubMed  CAS  Google Scholar 

  40. Yaqoob, P., Newsholme, E.A., and Calder, P.C. (1994) Inhibition of Natural Killer Cell Activity by Dietary Lipids,Immunol. Lett. 41, 241–247.

    Article  PubMed  CAS  Google Scholar 

  41. Mertin, J., Stackpole, A., and Shumway, S. (1985) Nutrition and Immunity: The Immunoregulatory Effect of n-6 Essential Fatty Acids Is Mediated Through Prostaglandin E,Int. Arch. Allergy Appl. Immunol. 77, 390–395.

    PubMed  CAS  Google Scholar 

  42. Hinds, A., and Sanders, T.A.B. (1993) The Effect of Increasing Levels of Dietary Fish Oil Rich in Eicosapentaenoic and Docosahexaenoic Acids on Lymphocyte Phospholipid Fatty Acid Composition and Cell-Mediated Immunity in the Mouse,Brit. J. Nutr. 69, 423–429.

    Article  PubMed  CAS  Google Scholar 

  43. Sanderson, P., Yaqoob, P., and Calder, P.C. (1995) Effects of Dietary Lipid Manipulation upon Graft vs. Host and Host vs. Graft Responses in the Rat,Cell. Immunol. 164, 240–247.

    Article  PubMed  CAS  Google Scholar 

  44. Report of the British Nutrition Foundation's Task Force (1992)Unsaturated Fatty Acids: Nutritional and Physiological Significance, Chapman and Hall, London.

  45. Yaqoob, P., Newsholme, E.A., and Calder, P.C. (1995) Influence of Cell Culture Conditions on Diet-Induced Changes in Lymphocyte Fatty Acid Composition,Biochim. Biophys. Acta 1255, 333–340.

    PubMed  Google Scholar 

  46. Allain, C.C., Poon, L.S., Chan, C.S.G., Richmond, W., and Fu, P.C. (1974) Enzymatic Determination of Total Serum Cholesterol,Clin. Chem. 20, 470–475.

    PubMed  CAS  Google Scholar 

  47. McGowan, M.W., Artiss, J.D., Strandbergh, D.R., and Zak, B. (1983) A Peroxidase-Coupled Method for the Colorimetric Determination of Serum Triglycerides,Clin. Chem. 29, 538–542.

    PubMed  CAS  Google Scholar 

  48. Calder, P.C., Yaqoob, P., Harvey, D.J., Watts, A., and Newsholme, E.A. (1994) The Incorporation of Fatty Acids by Lymphocytes and the Effect on Fatty Acid Composition and Membrane Fluidity,Biochem. J. 300, 509–518.

    PubMed  CAS  Google Scholar 

  49. Garg, M.L., Sebokova, E., Wierzbicki, A., Thomson, A.B.R., and Clandinin, M.T. (1988) Differential Effects of Dietary Linoleic and α-Linolenic Acid on Lipid Metabolism in Rat Tissues,Lipids 23, 847–852.

    PubMed  CAS  Google Scholar 

  50. Rustan, A.C., Christiansen, E.N., and Drevon, C.A. (1992) Serum Lipids, Hepatic Glycerolipid Metabolism and Peroxisomal Fatty Acid Oxidation in Rats Fed n-3 and n-6 Fatty Acids,Biochem. J. 283, 333–339.

    PubMed  CAS  Google Scholar 

  51. Leyton, J., Drury, P.J., and Crawford, M.A. (1987) Differential Oxidation of Saturated and Unsaturated Fatty Acidsin vivo in the Rat,Brit. J. Nutr. 57, 383–393.

    Article  PubMed  CAS  Google Scholar 

  52. Berthou, L., Saladin, R., Yaqoob, P., Branellec, D., Calder, P., Fruchart, J.-C., Denefle, P., Auwerx, J., and Staels, B. (1995) Regulation of Rat Liver Apolipoprotein A-I, Apolipoprotein A-II and Acyl CoA Oxidase Gene Expression by Fibrates and Dietary Fatty Acids,Eur. J. Biochem. 232, 179–187.

    Article  PubMed  CAS  Google Scholar 

  53. Sherrington, E.J., Yaqoob, P., and Calder, P.C. (1994) Differential Effects of High Fat Diets on Adipose Deposition in the Rat,Proc. Nutr. Soc. 53, 69A.

    Google Scholar 

  54. Meydani, S.N., Endres, S., Woods, M.M., Goldin, B.R., Soo, C., Morrill-Labrode, A., and Dinarello, C. (1991) Oral (n-3) Fatty Acid Supplementation Suppresses Cytokine Production and Lymphocyte Proliferation: Comparison Between Young and Older Women,J. nutr. 121, 547–555.

    PubMed  CAS  Google Scholar 

  55. Meydani, S.N., Lichtenstein, A.H., Cornwall, S., Meydani, M., Goldin, B.R., Rasmussen, H., Dinarello, C.A., and Schaefer, E.J. (1983) Immunologic Effects of National Cholesterol Education Panel Step-2 Diefs with and without Fish-Derived n-3 Fatty Acid Enrichment,J. Clin. Invest. 92, 105–113.

    Article  Google Scholar 

  56. Endres, S., Meydani, S.N., Ghorbani, R., Schindler, R., and Dinarello, C.A. (1993) Dietary Supplementation with n-3 Fatty Acids Suppresses Interleukin-2 Production and Mononuclear Cell Proliferation,J. Leuk. Biol. 54, 599–603.

    CAS  Google Scholar 

  57. Rola-Pleszczynski, M., Gagnon, L., and Sirois, P. (1983) Leukotriene B4 Augments Human Natural Cytotoxic Cell Activity,Biochem. Biophys. Res. Commun. 113, 531–537.

    Article  PubMed  CAS  Google Scholar 

  58. Hubbard, N.E., Chapkin, R.S., and Erickson, K.L. (1994) Effect of Dietary Linseed Oil on Tumoricidal Activity and Eicosanoid Production in Murine Macrophages,Lipids 29, 651–655.

    PubMed  CAS  Google Scholar 

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Jeffery, N.M., Sanderson, P., Sherrington, E.J. et al. The ratio of n-6 to n-3 polyunsaturated fatty acids in the rat diet alters serum lipid levels and lymphocyte functions. Lipids 31, 737–745 (1996). https://doi.org/10.1007/BF02522890

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