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Conjugated linoleic acid isomer effects in atherosclerosis: Growth and regression of lesions

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Lipids

Abstract

Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of octadecadienoic acid, has been shown to inhibit experimentally induced atherosclerosis in rabbits and also to cause significant regression of pre-established atheromatous lesions in rabbits. The two major CLA isomers (cis9,trans11 and trans10,cis12), now available at 90% purity, have been tested individually for their anti-atherogenic or lesion regression potency. The two major isomers and the mixture were fed for 90 d to rabbits fed 0.2% cholesterol. Atherosclerosis was inhibited significantly by all three preparations. The two CLA isomers and the isomer mix were also fed (1.0%) as part of a cholesterol-free diet for 90 d to rabbits bearing atheromatous lesions produced by feeding an atherogenic diet. A fourth group was maintained on a cholesterol-free diet. On the CLA-free diet atherosclerosis was exacerbated by 35%. Reduction of severity of atheromatous lesions was observed to the same extent in all three CLA-fed groups. The average reduction of severity in the three CLA-fed groups was 26±2% compared with the first control (atherogenic diet) and 46±1% compared with the regression diet. Insofar as individual effects on atherosclerosis were concerned, there was no difference between the CLA mix and the cis9,trans11 and trans10,cis12 isomers. They inhibit atherogenesis by 50% when fed as a component of a semipurified diet containing 0.2% cholesterol; and when fed as part of a cholesterol-free diet, they reduce established lesions by 26%. Reduction of atheromata to the observed extent by dietar means alone is noteworthy.

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Abbreviations

c9,t11 :

cis9,trans11 CLA

ICAM:

intercellular adhesion molecule

PGE2 :

prostaglandin E2

t10,c12 :

trans10,cis12 CLA

References

  1. Chin, S.F., Liu, W., Storkson, J.M., Ha, Y.L., and Pariza, M.W. (1992) Dietary Sources of Conjugated Dienoic Isomers of Linoleic Acid, a Newly Recognized Class of Anticarcinogens, J. Food Comp. Anal. 5, 185–197.

    Article  CAS  Google Scholar 

  2. Kritchevsky, D. (2000) Antimutagenic and Some Other Effects of Conjugated Linoleic Acid, Br. J. Nutr. 83, 459–465.

    PubMed  CAS  Google Scholar 

  3. Lee, K.N., Kritchevsky, D., and Pariza, M.W. (1994) Conjugated Linoleic Acid and Atherosclerosis in Rabbits, Atherosclerosis 108, 19–25.

    Article  PubMed  CAS  Google Scholar 

  4. Kritchevsky, D., Tepper, S.A., Wright, S., Tso, P., and Czarnecki, S.K. (2000) Influence of Conjugated Linoleic Acid (CLA) on Establishment and Progression of Atherosclerosis in Rabbits, J. Am. Coll. Nutr. 19, 472S-477S.

    PubMed  CAS  Google Scholar 

  5. Kritchevsky, D., Tepper, S.A., Wright, S., and Czarnecki, S.K. (2002) Influence of Graded Levels of Conjugated Linoleic Acid (CLA) on Experimental Atherosclerosis in Rabbits, Nutr. Res. 22, 1275–1279.

    Article  CAS  Google Scholar 

  6. Nicolosi, R.J., Rogers, E.J., Kritchevsky, D., Scimeca, J.A., and Huth, P.J. (1997) Dietary Conjugated Linoleic Reduces Plasma Lipoproteins and Early Aortic Atherosclerosis in Hypercholesterolemic Hamsters, Artery 22, 266–277.

    PubMed  CAS  Google Scholar 

  7. Wilson, T.A., Nicolosi, R.J., Chrysam, M. and Kritchevsky, D. (2000) Conjugated Linoleic Acid Reduces Early Atherosclerosis Greater Than Linoleic Acid in Hypercholesterolemic Hamsters, Nutr. Res. 20, 1795–1805.

    Article  CAS  Google Scholar 

  8. Munday, J.S., Thompson, K.G., and James, K.A.C. (1999) Dietary Conjugated Linoleic Acids Promote Fatty Streak Formation in the C57BL/6 Mouse Atherosclerosis Model, Br. J. Nutr. 81, 251–255.

    PubMed  CAS  Google Scholar 

  9. Park, Y., Albright, K.J., Liu, W., Storkson, J.M., Cook, M.E., and Pariza, M.W. (1997) Effect of Conjugated Linoleic Acid on Body Composition in Mice, Lipids 32, 853–858.

    Article  PubMed  CAS  Google Scholar 

  10. Park, Y., Storkson, J.M., Albright, K.J., Liu, W., and Pariza, M.W. (1999) Evidence That the trans-10,cis-12 Isomer of Conjugated Linoleic Acid Induces Body composition Changes in Mice, Lipids 34, 235–241.

    Article  PubMed  CAS  Google Scholar 

  11. Evans, M.E., Brown, J.M., and McIntosh, M.K. (2002) Isomer Specific Effects of Conjugated Linoleic Acid (CLA) on Adiposity and Lipid Metabolism, J. Nutr. Biochem. 13, 508–516.

    Article  PubMed  CAS  Google Scholar 

  12. Risérus, U., Arner, P., Brismar, K., and Vessby, B. (2002) Treatment with Dietary trans10,cis12 Conjugated Linoleic Acid Causes Isomer-Specific Insulin Resistance in Obese Men with Metabolic Syndrome, Diabetes Care, 25, 1516–1521.

    PubMed  Google Scholar 

  13. Risérus, V., Basu, S., Jovinge, S., Fredrikson, G.N., Ärnlöv, J., and Vessby, B. (2002) Supplementation with Conjugated Linoleic Acid Causes Isomer-Dependent Oxidative Stress and Elevated C-Reactive Protein. A Potential Link to Fatty Acid-Induced Insulin Resistance, Circulation 106, 1925–1929.

    Article  PubMed  Google Scholar 

  14. Clément, L., Porrier, H., Niot, I., Bocher, V., Guerre-Milo, M., Krief, S., Staels, B., and Besnard, P. (2002) Dietary trans10,cis12 Conjugated Linoleic Acid Induces Hyperinsulinemia and Fatty Liver in the Mouse, J. Lipid Res. 43, 1400–1409.

    Article  PubMed  CAS  Google Scholar 

  15. Roche, H.M., Noone, E., Sewter, C., McBennett, S., Savage, D., Gibney, M.J., O'Rahilly, S.O., and Vidal-Piug, J. (2002) Isomer-Dependent Metabolic Effects of Conjugated Linoleic Acid: Insights from Molecular Markers Sterol Regulatory Element-Binding Protein-1c and LXRα, Diabetes 51, 2037–2044.

    PubMed  CAS  Google Scholar 

  16. Kang, K., and Pariza, M.W. (2001) Trans10,cis12-Conjugated Linoleic Acid Reduces Leptin Secretion from 3T3-L1 Adipocytes, Biochem. Biophys. Res. Commun. 287, 377–382.

    Article  PubMed  CAS  Google Scholar 

  17. Brown, J.M., Halvorsen, Y.D., Lea-Currie, Y.R., Geigerman, C., and McIntosh, M. (2001) Trans10,cis12 but Not cis9,trans11, Conjugated Linoleic Acid Attenuates Lipogenesis in Primary Cultures of Stromal Vascular Cells from Human Adipose Tissue, J. Nutr. 131, 2316–2321.

    PubMed  CAS  Google Scholar 

  18. Lin, Y., Kreeft, A., Schuurbiers, A.E., and Draijer, R. (2001) Different Effects of Conjugated Linoleic Isomers on Lipoprotein Lipase Activity in 3T3-L1 Adipocytes, J. Nutr. Biochem. 12, 183–189.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  20. DeHoff, J.L., Davidson, L.M., and Kritchevsky, D. (1978) An Enzymatic Assay for Determinations of Free and Total Cholesterol in Tissue, Clin. Chem. 24, 433–435.

    CAS  Google Scholar 

  21. Wilson, T.A., Nicolosi, R.J., Rogers, E.J., Sacchiero, R., and Goldberg, D.J. (1998) Studies of Cholesterol and Bile Acid Metabolism, and Early Atherogenesis in Hamsters Fed GT16-239 a Novel Bile Acid Sequestran, Atherosclerosis 140, 315–324.

    Article  PubMed  CAS  Google Scholar 

  22. Duff, G.L., and McMillan, G.C. (1949) The Effect of Alloxan Diabetes on Experimental Atherosclerosis in Rabbits, J. Exp. Med. 89, 611–630.

    Article  CAS  PubMed  Google Scholar 

  23. Wei, W., Li, C., Wang, Y., Su, H., Zhu, J., and Kritchevsky, D. (2003) Hypolipidemic and Anti-atherogenic Effects of Long-Term Cholestin (Monascus purpureus-fermented rice, red yeast rice) in Cholesterol-Fed Rabbits, J. Nutr. Biochem. 14, 314–318.

    Article  PubMed  CAS  Google Scholar 

  24. Klurfeld, D.M. (2002) Kidney and Bladder Stones in Rodents Fed Purified Diets, J. Nutr. 132, 3784.

    PubMed  CAS  Google Scholar 

  25. McMillan, G.C., Horlick, L., and Duff, G.L. (1955) Cholesterol Content of Aorta in Relation to Severity of Atherosclerosis. Studies During Progression and Retrogression of Experimental Lesions, Arch. Pathol. 59, 285–290.

    CAS  Google Scholar 

  26. Kritchevsky, D., and Tepper, S.A. (1962) Cholesterol Vehicle in Experimental Atherosclerosis. 5. Influence of Fats and Fatty Acids on Pre-established Atheromata, J. Atheroscler. Res. 2, 471–477.

    PubMed  CAS  Google Scholar 

  27. Kritchevsky, D., Tepper, S.A., and Story, J.A. (1978) Cholesterol Vehicle in Experimental Atherosclerosis. 16. Effect of Peanut Oil on Pre-established Lesions, Atherosclerosis 31, 365–370.

    Article  PubMed  CAS  Google Scholar 

  28. Beher, W.T., Anthony, W.L., and Baker, G.D. (1956) Effects of Beta Sitosterol on Regression of Cholesterol Atherosclerosis in Rabbits, Circulation Res. 4, 485–487.

    PubMed  CAS  Google Scholar 

  29. Beher, W.T., Baker, G.D. and Anthony, W.L. (1957) Effect of Dehydrocholesterol and Beta-Sitosterol on Cholesterol Atheroscherosis in Rabbits, Circulation Res. 5, 202–206.

    PubMed  CAS  Google Scholar 

  30. Kritchevsky, D., Sallata, P., and Tepper, S.A. (1968) Influence of Ethyl p-Chlorophenoxyisobutyrate (CPIB) upon Establishment and Progression of Experimental Atherosclerosis in Rabbits, J. Atheroscler. Res. 8, 755–761.

    PubMed  CAS  Google Scholar 

  31. Kritchevsky, D., Moynihan, J.L., Langan, J., Tepper, S.A., and Sachs, M.L. (1961) Effects of d- and l-Thyroxine and d- and l-3,5,3′-Tricodothyronine on Development and Regression of Experimental Atherosclerosis in Rabbits, J. Atheroscler. Res. 1, 211–221.

    Article  PubMed  CAS  Google Scholar 

  32. Kano, H., Hayashi, T., Sumi, D., Esaki, T., Asai, Y., Thankur, N.K., Jayachandran, M., and Iguchi, A. (1999) A HMG-CoA Reductase Inhibitor Improved Regression of Atherosclerosis in the Rabbit Aorta Without Affecting Serum Lipid Levels: Possible Relevance to Up-Regulation of Endothelial NO Synthetase mRNA, Biochem. Biophys. Res. Commun. 259, 414–419.

    Article  PubMed  CAS  Google Scholar 

  33. Badimon, J.J., Badimon, L., and Fuster, V. (1990) Regression of Atherosclerotic Lesions by High Density Lipoprotein Plasma Fraction in the Cholesterol-Fed Rabbit, J. Clin. Invest. 85, 1234–1241.

    Article  PubMed  CAS  Google Scholar 

  34. Constantinides, P., and Gutmann-Auersperg, N. (1960) Inhibition of Progress of Pre-established Atherosclerosis by Diethylstilbesterol in Rabbits, Arch. Pathol. 70, 35–42.

    PubMed  CAS  Google Scholar 

  35. Vesselinovitch, D., Wissler, R.W., Fisher-Dzoga, K., Hughes, R., and Dubien, L. (1974) Regression of Atherosclerosis in Rabbits. 1. Treatment with Low-Fat Diet, Hyperoxia and Hypolipidemic Agents, Atherosclerosis 19, 259–275.

    Article  PubMed  CAS  Google Scholar 

  36. Khosla, P., and Rungwe, T.V. (2001) Conjugated Linoleic Acid: Effects on Plasma Lipids and Cardiovascular Function, Curr. Opin. Lipidol. 12, 31–34.

    Article  PubMed  CAS  Google Scholar 

  37. Ip, C., Chim, S.F., Scimeca, J.A., and Pariza, M.W. (1991) Mammary Cancer Prevention by Conjugated Dienoic Derivatives of Linoleic Acid, Cancer Res. 51, 6118–6124.

    PubMed  CAS  Google Scholar 

  38. Ha, Y.L., Storkson, J., and Pariza, M.W. (1990) Inhibition of Benzo(a)pyrene-Induced Mouse Forestomach Neoplasia by Conjugated Dienoic Derivatives of Linoleic Acid, Cancer Res. 50, 1097–1101.

    PubMed  CAS  Google Scholar 

  39. Kim, D.N., Ho, H.T., Lawrence, D.A., Schmee, J., and Thomas, W.A. (1989) Modification of Lipoprotein Patterns and Retardation of Atherosclerosis by a Fish Oil Supplement to a Hyperlipidemic Diet for Swine, Atherosclerosis 76, 35–54.

    Article  PubMed  CAS  Google Scholar 

  40. Sugano, M., Tsujita, A., Yamasaki, M., Yamada, K., Ikeda, I., and Kritchevsky, D. (1997) Lymphatic Recovery, Tissue Distribution, and Metabolic Effects of Conjugated Linoleic Acid in Rats, J. Nutr. Biochem. 8, 34–43.

    Article  Google Scholar 

  41. van den Berg, J.J., Cook, N.E., and Tribble, D.L. (1995) Reinvestigation of the Antioxidant Properties of Conjugated Linoleic Acid, Lipids 30, 599–605.

    PubMed  Google Scholar 

  42. Banni, S., Angioni, E., Contini, M.S., Carta, G., Casu, V., Iengo, G.A., Melis, M.P., Deiana, M., Dessi, M.A., and Corongiu, F.P. (1998) Conjugated Linoleic Acid and Oxidative Stress, J. Am. Oil Chem. Soc. 75, 261–267.

    CAS  Google Scholar 

  43. Stangl, G.I. (2000) High Dietary Levels of a Conjugated Linoleic Acid Mixture After Hepatic Glycerophospholipid Class Profile and Cholesterol-Carrying Serum Lipoproteins in Rats, J. Nutr. Biochem. 11, 184–191.

    Article  PubMed  CAS  Google Scholar 

  44. Banni, S. (2002) Conjugated Linoleic Acid Metabolism, Curr. Opin. Lipidol. 13, 261–266.

    Article  PubMed  CAS  Google Scholar 

  45. Liu, K.L., and Belury, M.A. (1998) Conjugated Linoleic Acid Reduces Arachidonic Acid Content and PGE2 Synthesis in Murine Keratinocytes, Cancer Lett. 127, 15–22.

    Article  PubMed  CAS  Google Scholar 

  46. Kavanaugh, C.J., Liu, K.L., and Belury, M.A. (1999) Effect of Dietary Conjugated Linoleic Acid on Phorbol Ester-Induced PGE2 Production and Hyperplasia in Mouse Epidermis, Nutr. Cancer 33, 132–138.

    Article  PubMed  CAS  Google Scholar 

  47. Crosby, A.J., Wahle, K.W.J., and Duthie, G.G. (1996) Modulation of Glutathione Peroxidase Activity in Human Vascular Endothelial Cells by Fatty Acids and the Cytokine, Interleukin 1β, Biochim. Biophys. Acta 1303, 187–192.

    PubMed  Google Scholar 

  48. Cesano, A., Visonneau, S., Scimeca, J.A., Kritchevsky, D., and Santoli, D. (1998) Opposite Effects of Linoleic Acid and Conjugated Linoleic Acid on Human Prostatic Cancer in SCID Mice, Anticancer Res. 18, 833–838.

    Google Scholar 

  49. Lusis, A.J. (2000) Atherosclerosis, Nature 407, 233–241.

    Article  PubMed  CAS  Google Scholar 

  50. Libby, P. (2002) Inflammation in Atherosclerosis, Nature 420, 868–874.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Chemistry, Chestnut Hill College, 19118, Pennsylvania, Philadelphia

    Susanne K. Czarnecki

  2. Department of Health and Clinical Sciences, University of Massachusetts-Lowell, 01854, Massachusetts, Lowell

    Thomas A. Wilson & Robert J. Nicolosi

  3. The Wistar Institute, 3601 Spruce St., 19104, Philadelphia, PA

    David Kritchevsky, Shirley A. Tepper & Scott Wright

Authors
  1. David Kritchevsky
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  2. Shirley A. Tepper
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  3. Scott Wright
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  4. Susanne K. Czarnecki
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  5. Thomas A. Wilson
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  6. Robert J. Nicolosi
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Correspondence to David Kritchevsky.

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Kritchevsky, D., Tepper, S.A., Wright, S. et al. Conjugated linoleic acid isomer effects in atherosclerosis: Growth and regression of lesions. Lipids 39, 611–616 (2004). https://doi.org/10.1007/s11745-004-1273-8

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  • DOI: https://doi.org/10.1007/s11745-004-1273-8

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