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Unique phospholipid metabolism in mouse heart in response to dietary docosahexaenoic or α-linolenic acids

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Lipids

Abstract

Diet and fatty acid metabolism interact in yet unknown ways to modulate membrane fatty acid composition and certain cellular functions. For example, dietary precursors or metabolic products of n-3 fatty acid metabolism differ in their ability to modify specific membrane components. In the present study, the effect of dietary 22∶6n−3 or its metabolic precursor, 18∶3n−3, on the selective accumulation of 22∶6n−3 by heart was investigated. The mass and fatty acid compositions of individual phospholipids (PL) in heart and liver were quantified in mice fed either 22∶6n−3 (from crocodile oil) or 18∶3n−3 (from soybean oil) for 13 wk. This study was conducted to determine if the selective accumulation of 22∶6n−3 in heart was due to the incorporation of 22∶6n−3 into cardiolipin (CL), a PL most prevalent in heart and known to accumulate 22∶6n−3. Although heart was significantly enriched with 22∶6n−3 relative to liver, the accumulation of 22∶6n−3 by CL in heart could not quantitatively account for this difference. CL from heart did accumulate 22∶6n−3, but only in mice fed preformed 22∶6n−3. Diets rich in non-22∶6n−3 fatty acids result in a fatty acid composition of phosphatidylcholine (PC) in heart that is unusually enriched with 22∶6n−3. In this study, the mass of PC in heart was positively correlated with the enrichment of 22∶6n−3 into PC. The increased mass of PC was coincident with a decrease in the mass of phosphatidylethanolamine, suggesting that 22∶6n−3 induced PC synthesis by increasing phosphatidylethanolamine-N-methyltransferase activity in the heart.

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Abbreviations

CE:

cholesterol ester

CL:

cardiolipin

CRO:

crocodile oil

FFA:

free fatty acid

PC:

phosphatidylcholine

PE:

phosphatidylethanolamine

PEMT:

phosphatidylethanolamine-N-methyltransferase

PL:

phospholipids

SO:

soybean oil

TG:

triacylglyceride

TLC:

thin-layer chromatography

References

  1. Yang, B.C., Saldeen, T.G., Bryant, J.L., Nichols, W.W., and Mehta, J.L. (1993) Long-Term Dietary Fish Oil Supplementation Protects Against Ischemia-Reperfusion-Induced Myocardial Dysfunction in Isolated Rat Hearts, Am. Heart J. 126, 1287–1292.

    Article  PubMed  CAS  Google Scholar 

  2. Yang, B., Saldeen, T.G., Nichols, W.W., and Mehta, J.L. (1993) Dietary Fish Oil Supplementation Attenuates Myocardial Dysfunction and Injury Caused by Global Ischemia and Reperfusion in Isolated Rat Hearts, J. Nutr. 123, 2067–2074.

    PubMed  CAS  Google Scholar 

  3. Hock, C.E., Beck, L.D., Bodine, R.C., and Reibel, D.K. (1990) Influence of Dietary n-3 Fatty Acids on Nyocardial Ischemia and Reperfusion, Am. J. Physiol. 259, H1518–1526.

    PubMed  CAS  Google Scholar 

  4. McLennan, P.L., Bridle, T.M., Abeywardena, M.Y., and Charnock, J.S. (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, 666–669.

    PubMed  CAS  Google Scholar 

  5. Pepe, S., and McLennan, P.L. (1996) Dietary Fish Oil Confers Direct Antiarrhythmic Properties on the Myocardium of Rats, J. Nutr. 126, 34–42.

    PubMed  CAS  Google Scholar 

  6. Leaf, A. (1995) Omega-3 Fatty Acids and Prevention of Ventricular Fibrillation, Prostaglandins Leukotrienes Essent. Fatty Acids 52, 197–198.

    Article  CAS  Google Scholar 

  7. Hayashi, M., Nasa, Y., Tanonaka, K., Sasaki, H., Miyake, R., Hayashi, J.-I., and Takeo, S. (1995) The Effects of Long-Term Treatment with Eicosapentaenoic Acid and Docosahexaenoic Acid on Hypoxia/Reoxygenation Injury of Isolated Cardiac Cells in Adults Rats, J. Mol. Cell Cardiol. 27, 2031–2041.

    Article  PubMed  CAS  Google Scholar 

  8. Grynberg, A., Fournier, A., Sergiel, J.-P., and Athias, P. (1996) Membrane Docosahexaenoic Acid vs. Eicosapentaenoic Acid and the Beating Function of the Cardiomyocyte and Its Regulation Through the Adrenergic Receptors, Lipids 31, S205-S210.

    PubMed  CAS  Google Scholar 

  9. McLennan, P., Howe, P., Abeywardena, M., Muggli, R., Raederstorff, D., Mano, M., Rayner, T., and Head, R. (1996) The Cardiovascular Protective Role of Docosahexaenoic Acid, Eur. J. Pharm. 300, 83–89.

    Article  CAS  Google Scholar 

  10. Mori, T.A., Bao, D.Q., Burke, V., Puddey, I.B., and Beilin, L.J. (1999) Docosahexaenoic Acid but Not Eicosapentaenoic Acid Lowers Ambulatory Blood Pressure and Heart Rate in Humans, Hypertension (Baltimore) 34, 253–260.

    CAS  Google Scholar 

  11. Grimsgaard, S., Bonaa, K.H., Hansen, J.-B., and Myhre, E.S.P. (1998) Effects of Highly Purified Eicosapentaenoic Acid and Docosahexaenoic Acid on Hemodynamics in Humans, Am. J. Clin. Nutr. 68, 52–59.

    PubMed  CAS  Google Scholar 

  12. Berger, A., Gershwin, M.E., and German, J.B. (1992) Effects of Various Dietary Fats on Cardiolipin Acyl Composition During Ontogeny of Mice, Lipids 27, 605–612.

    PubMed  CAS  Google Scholar 

  13. Al Makdessi, S., Sweidan, H., and Jacob, R. (1994) n-3 versus n-6 Fatty Acid Incorporation into the Phospholipids of Rat Heart Sarcolemma: A Comparative Study of Four Different Oil Diets, J. Mol. Cell. Cardiol. 26, 23–29.

    Article  PubMed  Google Scholar 

  14. Charnock, J.S., Abeywardena, M.Y., and McLennan, P.L. (1986) Comparative Changes in the Fatty-Acid Composition of Rat Cardiac Phospholipids After Long-Term Feeding of Sunflower Seed Oil- or Tuna Fish Oil-Supplemented Diets, Ann. Nutr. Metab. 30, 393–406.

    Article  PubMed  CAS  Google Scholar 

  15. Gudbjarnason, S., and Oskarsdottir, G. (1977) Modification of Fatty Acid Composition of Rat Heart Lipids by Feeding Cod Liver Oil, Biochim. Biophys. Acta 487, 10–15.

    PubMed  CAS  Google Scholar 

  16. Iritani, N., and Fujikawa, S. (1982) Competitive Incorporation of Dietary Omega-3 and Omega-6 Polyunsaturated Fatty Acids into the Tissue Phospholipids in Rats, J. Nutr. Sci. Vitaminol. 28, 621–629.

    PubMed  CAS  Google Scholar 

  17. Poorthuis, B.J., Yazaki, P.J., Hostetler, K.Y. (1976) An Improved Two-Dimensional Thin-Layer Chromatography System for the Separation of Phosphatidylglycerol and Its Derivatives, J. Lipid Res. 17, 433–437.

    PubMed  CAS  Google Scholar 

  18. Hatch, G.M. (1996) Regulation of Cardiolipin Biosynthesis in the Heart, Mol. Cell. Biochem. 159, 139–148.

    Article  PubMed  CAS  Google Scholar 

  19. Watkins, S.M., Carter, L.C., and German, J.B. (1998) Docosahexaenoic Acid Accumulates in Cardiolipin and Enhances HT-29 Cell Oxidant Production, J. Lipid Res. 39, 1583–1588.

    PubMed  CAS  Google Scholar 

  20. Hinrichs, S.H., Nerenberg, M., Reynolds, R.K., Khoury, G., and Jay, G. (1987) A Transgenic Mouse Model for Human Neurofibromatosis, Science 237, 1340–1343.

    Article  PubMed  CAS  Google Scholar 

  21. Walzem, R.L., and Clifford, A.J. (1988) Folate Deficiency in Rats Fed Diets Containing Free Amino Acids or Intact Proteins, J. Nutr. 118, 1089–1096.

    PubMed  CAS  Google Scholar 

  22. Ruiz, J.I., and Ochoa, B. (1997) Quantification in the Subnanomolar Range of Phospholipids and Neutral Lipids by Monodimensional Thin-Layer Chromatography and Image Analysis, J. Lipid Res. 38, 1482–1489.

    PubMed  CAS  Google Scholar 

  23. Folch, J., Lee, M., and Sloane-Stanley, G.H. (1957) A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissues, J. Biol. Chem. 226, 497–509.

    PubMed  CAS  Google Scholar 

  24. Holub, B.J., and Skeaf, C.M. (1987) Nutritional Regulation of Cellular Phosphatidylinositol, in Methods in Enzymology (Conn, P.M., ed.), pp. 234–243, Academic Press, Inc., Orlando.

    Google Scholar 

  25. Mangold, H.K. (1969) Thin-Layer Chromatography—A Laboratory Handbook, pp. 11–25, Springer-Verlag, New York.

    Google Scholar 

  26. Kramer, J.K. (1980) Comparative Studies on Composition of Cardiac Phospholipids in Rats Fed Different Vegetable Oils, Lipids 15, 651–660.

    PubMed  CAS  Google Scholar 

  27. Swanson, J.E., and Kinsella, J.E. (1986) Dietary n-3 Polyunsaturated Fatty Acids: Modification of Rat Cardiac Lipids and Fatty Acid Composition, J. Nutr. 116, 514–523.

    PubMed  CAS  Google Scholar 

  28. Madsen, L., Froyland, L., Dyroy, E., Helland, K., and Berge, R.K. (1998) Docosahexaenoic and Eicosapentaenoic Acids Are Differently Metabolized in Rat Liver During Mitochondria and Peroxisome Proliferation, J. Lipid Res. 39, 583–593.

    PubMed  CAS  Google Scholar 

  29. Yamaoka, S., Urade, R., and Kito, M. (1988) Mitochondrial Function in Rats Is Affected by Modification of Membrane Phospholipids with Dietary Sardine Oil, J. Nutr. 118, 290–296.

    PubMed  CAS  Google Scholar 

  30. Voss, A., Reinhart, M., Sankarappa, S., and Sprecher, H. (1991) 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. 266, 19995–20000.

    PubMed  CAS  Google Scholar 

  31. Moore, S.A., Hurt, E., Yoder, E., Sprecher, H., and Spector, A.A. (1995) Docosahexaenoic Acid Synthesis in Human Skin Fibroblasts Involves Peroxisomal Retroconversion of Tetracosahexaenoic Acid, J. Lipid Res. 36, 2433–2443.

    PubMed  CAS  Google Scholar 

  32. Sprecher, H., and Chen, Q. (1999) Polyunsaturated Fatty Acid Biosynthesis: A Microsomal-Peroxisomal Process, Prostaglandins Leukotrienes Essent. Fatty Acids 60, 317–321.

    Article  CAS  Google Scholar 

  33. Sprecher, H., Luthria, D.L., Mohammed, B.S., and Baykousheva, S.P. (1995) Reevaluation of the Pathways for the Biosynthesis of Polyunsaturated Fatty Acids, J. Lipid Res. 36, 2471–2477.

    PubMed  CAS  Google Scholar 

  34. Baykousheva, S.P., Luthria, D.L., and Sprecher, H. (1995) Peroxisomal Microsomal Communication in Unsaturated Fatty Acid Metabolism, FEBS Lett. 367, 198–200.

    Article  PubMed  CAS  Google Scholar 

  35. Ma, B.J., Taylor, W.A., Dolinsky, V.W., and Hatch, G.M. (1999) Acylation of Monolysocardiolipin in Rat Heart, J. Lipid Res. 40, 1837–1845.

    PubMed  CAS  Google Scholar 

  36. Schlame, M., and Rustow, B. (1990) Lysocardiolipin Formation and Reacylation in Isolated Rat Liver Mitochondria, Biochem. J. 272, 589–595.

    PubMed  CAS  Google Scholar 

  37. Schlame, M., and Haldar, D. (1993) Cardiolipin Is Synthesized on the Matrix Side of the Inner Membrane in Rat Liver Mitochondria, J. Biol. Chem. 268, 74–79.

    PubMed  CAS  Google Scholar 

  38. Vance, D.E. (1996) Glycerolipid Biosynthesis in Eukaryotes, in Biochemistry of Lipids, Lipoproteins and Membranes (Vance, D.E., and Vance, J., eds.), Vol. 31, pp. 153–181, Elsevier, Amsterdam.

    Google Scholar 

  39. Kennedy, E.P. (1989) Discovery of the Pathways for the Biosynthesis of Phosphatidylcholine, in Phosphatidylcholine Metabolism (Vance, D.E., ed.), pp. 1–9, CRC Press, Boca Raton.

    Google Scholar 

  40. Hargreaves, K.M., Pehowich, D.J., and Clandinin, M.T. (1989) Effect of Dietary Lipid Composition on Rat Liver Microsomal Phosphatidylcholine Synthesis, J. Nutr. 119, 344–348.

    PubMed  CAS  Google Scholar 

  41. Mallampalli, R.K., Salome, R.G., and Spector, A.A. (1994) Regulation of CTP: Choline-Phosphate Cytidylyltransferase by Polyunsaturated n-3 Fatty Acids, Am. J. Physiol. 267, L641-L648.

    PubMed  CAS  Google Scholar 

  42. Baybutt, R.C., Smith, J.E., and Yeh, Y.Y. (1993) The Effects of Dietary Fish Oil on Alveolar Type II Cell Fatty Acids and Lung Surfactant Phospholipids, Lipids 28, 167–172.

    PubMed  CAS  Google Scholar 

  43. Samborski, R.W., Ridgway, N.D., and Vance, D.E. (1990) Evidence That Only Newly Made Phosphatidylethanolamine Is Methylated to Phosphatidylcholine and That Phosphatidylethanolamine Is Not Significantly Decaylated-Reacylated in Rat Hepatocytes, J. Biol. Chem. 265, 18322–18329.

    PubMed  CAS  Google Scholar 

  44. Ridgway, N.D., and Vance, D.E. (1988) Specificity of Rat Hepatic Phosphatidylethanolamine N-Methyltransferase for Molecular Species of Diacyl Phosphatidylethanolamine, J. Biol. Chem. 263, 16856–16863.

    PubMed  CAS  Google Scholar 

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Correspondence to S. M. Watkins.

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Watkins, S.M., Lin, T.Y., Davis, R.M. et al. Unique phospholipid metabolism in mouse heart in response to dietary docosahexaenoic or α-linolenic acids. Lipids 36, 247–254 (2001). https://doi.org/10.1007/s11745-001-0714-8

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  • DOI: https://doi.org/10.1007/s11745-001-0714-8

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