Nutr Res Pract.  2008 Dec;2(4):326-330. 10.4162/nrp.2008.2.4.326.

Isomer specificity of conjugated linoleic acid (CLA): 9E,11E-CLA

• Lee Y

• KMID: 2139211
• DOI: http://doi.org/10.4162/nrp.2008.2.4.326

Abstract

Conjugated linoleic acids (CLA) were identified in 1980's, since then it has been intensively studied due to its various beneficial health effects such as anti-inflammatory, anti-atherogenic, anti-carcinogenic and anti-diabetic/obesity effects. Isomer specificity of a number of CLA isomers, especially predominant isomer 9Z,11E- and 10E,12Z-CLA, is now recognized. However, the less prevalent CLA isomers have not been well characterized. Recently, studies have reported the distinctively different effects of 9E,11E-CLA in colon cancer cells, endothelial cells, and macrophage cells compared to the rest of CLA isomers. In this review, various effects of CLAs, especially anti-inflammatory and anti-atherogenic effects, will be discussed with focusing on the isomer-specific effects and potential mechanism of action of CLA. At last, recent studies about 9E,11E-CLA in in vitro and animal models will be discussed.

Keyword

Conjugated linoleic acid (CLA); 9E,11E-CLA; anti-inflammatory; isomer-specificity

MeSH Terms

Colonic Neoplasms
Endothelial Cells
Linoleic Acid
Linoleic Acids, Conjugated
Macrophages
Models, Animal
Sensitivity and Specificity*
Linoleic Acid
Linoleic Acids, Conjugated

Reference

1. Albers R, van der Wielen RP, Brink EJ, Hendriks HF, Dorovska-Taran VN, Mohede IC. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men. Eur J Clin Nutr. 2003. 57:595–603.

2. Al-Madaney MM, Kramer JK, Deng Z, Vanderhoek JY. Effects of lipid-esterified conjugated linoleic acid isomers on platelet function: evidence for stimulation of platelet phospholipase activity. Biochim Biophys Acta. 2003. 1635:75–82.

3. Arbones-Mainar JM, Navarro MA, Guzman MA, Arnal C, Surra JC, Acin S, Carnicer R, Osada J, Roche HM. Selective effect of conjugated linoleic acid isomers on atherosclerotic lesion development in apolipoprotein E knockout mice. Atherosclerosis. 2006. 189:318–327.

4. Benito P, Nelson GJ, Kelley DS, Bartolini G, Schmidt PC, Simon V. The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids. 2001. 36:229–236.

5. Beppu F, Hosokawa M, Tanaka L, Kohno H, Tanaka T, Miyashita K. Potent inhibitory effect of trans9, trans11 isomer of conjugated linoleic acid on the growth of human colon cancer cells. J Nutr Biochem. 2006. 17:830–836.

6. Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G. Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem. 2006. 17:789–810.

7. Calder PC, Grimble RF. Polyunsaturated fatty acids, inflammation and immunity. Eur J Clin Nutr. 2002. 56:S14–S19.

8. Cheng WL, Lii CK, Chen HW, Lin TH, Liu KL. Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-kappaB pathway. J Agric Food Chem. 2004. 52:71–78.

9. Coen P, Cummins P, Birney Y, Devery R, Cahill P. Modulation of nitric oxide and 6-keto-prostaglandin F(1alpha) production in bovine aortic endothelial cells by conjugated linoleic acid. Endothelium. 2004. 11:211–220.

10. Cook ME, Miller CC, Park Y, Pariza M. Immune modulation by altered nutrient metabolism: nutritional control of immune-induced growth depression. Poult Sci. 1993. 72:1301–1305.

11. Cuzzocrea S, Pisano B, Dugo L, Ianaro A, Maffia P, Patel NS, Di Paola R, Ialenti A, Genovese T, Chatterjee PK, Di Rosa M, Caputi AP, Thiemermann C. Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-gamma, reduces acute inflammation. Eur J Pharmacol. 2004. 483:79–93.

12. Desroches S, Chouinard PY, Galibois I, Corneau L, Delisle J, Lamarche B, Couture P, Bergeron N. Lack of effect of dietary conjugated linoleic acids naturally incorporated into butter on the lipid profile and body composition of overweight and obese men. Am J Clin Nutr. 2005. 82:309–319.

13. Ecker J, Langmann T, Moehle C, Schmitz G. Isomer specific effects of Conjugated Linoleic Acid on macrophage ABCG1 transcription by a SREBP-1c dependent mechanism. Biochem Biophys Res Commun. 2007. 352:805–811.

14. Evans M, Brown J, McIntosh M. Isomer-specific effects of conjugated linoleic acid (CLA) on adiposity and lipid metabolism. J Nutr Biochem. 2002. 13:508.

15. Gaullier JM, Berven G, Blankson H, Gudmundsen O. Clinical trial results support a preference for using CLA preparations enriched with two isomers rather than four isomers in human studies. Lipids. 2002. 37:1019–1025.

16. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am J Clin Nutr. 2004. 79:1118–1125.

17. Hayek MG, Han SN, Wu D, Watkins BA, Meydani M, Dorsey JL, Smith DE, Meydani SN. Dietary conjugated linoleic acid influences the immune response of young and old C57BL/6NCrlBR mice. J Nutr. 1999. 129:32–38.

18. Huang YC, Luedecke LO, Shultz TD. Effect of cheddar cheese consumption on plasma conjugated linoleic acid concentrations in men. Nutr Res. 1994. 14:373–386.

19. Ip C, Scimeca JA, Thompson HJ. Conjugated linoleic acid. A powerful anticarcinogen from animal fat sources. Cancer. 1994. 74:1050–1054.

20. Jaudszus A, Foerster M, Kroegel C, Wolf I, Jahreis G. Cis-9,Trans-11-CLA exerts anti-inflammatory effects in human bronchial epithelial cells and eosinophils: Comparison to Trans-10,Cis-12-CLA and to linoleic acid. Biochim Biophys Acta. 2005. 1737:111–118.

21. Kelley DS, Taylor PC, Rudolph IL, Benito P, Nelson GJ, Mackey BE, Erickson KL. Dietary conjugated linoleic acid didnot alter immune status in young healthy women. Lipids. 2000. 35:1065–1071.

22. Kelley DS, Warren JM, Simon VA, Bartolini G, Mackey BE, Erickson KL. Similar effects of c9,t11-CLA and t10, c12-CLA on immune cell functions in mice. Lipids. 2002. 37:725–728.

23. Kelly GS. Conjugated linoleic acid: a review. Altern Med Rev. 2001. 6:367–382.

24. Kishino S, Ogawa J, Ando A, Iwashita T, Fujita T, Kawashima H, Shimizu S. Structural analysis of conjugated linoleic acid produced by Lactobacillus plantarum, and factors affecting isomer production. Biosci Biotechnol Biochem. 2003. 67:179–182.

25. Kishino S, Ogawa J, Ando A, Omura Y, Shimizu S. Ricinoleic acid and castor oil as substrates for conjugated linoleic acid production by washed cells of Lactobacillus plantarum. Biosci Biotechnol Biochem. 2002. 66:2283–2286.

26. Kramer JK, Parodi PW, Jensen RG, Mossoba MM, Yurawecz M, Adlof RO. Rumenic acid: a proposed common name for the major conjugated linoleic acid isomer found in natural products. Lipids. 1998. 33:835.

27. Kritchevsky D, Tepper SA, Wright S, Tso P, Czarnecki SK. Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits. J Am Coll Nutr. 2000. 19:472S–477S.

28. Lai KL, Torres-Duarte AP, Vanderhoek JY. 9-trans, 11-trans-CLA: antiproliferative and proapoptotic effects on bovine endothelial cells. Lipids. 2005. 40:1107–1116.

29. Lee KN, Kritchevsky D, Pariza MW. Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis. 1994. 108:19–25.

30. Lee Y, Thompson JT, de Lera AR, Vanden Heuvel JP. Isomer-specific effects of conjugated linoleic acid on gene expression in RAW 264.7. J Nutr Biochem. 2008. 5:[Epub ahead of print].

31. Li Y, Watkins BA. Conjugated linoleic acids alter bone fatty acid composition and reduce ex vivo prostaglandin E2 biosynthesis in rats fed n-6 or n-3 fatty acids. Lipids. 1998. 33:417–425.

32. Loscher CE, Draper E, Leavy O, Kelleher D, Mills KH, Roche HM. Conjugated linoleic acid suppresses NF-kappa B activation and IL-12 production in dendritic cells through ERK-mediated IL-10 induction. J Immunol. 2005. 175:4990–4998.

33. Luongo D, Bergamo P, Rossi M. Effects of conjugated linoleic acid on growth and cytokine expression in Jurkat T cells. Immunol Lett. 2003. 90:195–201.

34. Mitchell PL, Langille MA, Currie DL, McLeod RS. Effect of conjugated linoleic acid isomers on lipoproteins and atherosclerosisin the Syrian Golden hamster. Biochim Biophys Acta. 2005. 1734:269–276.

35. Mougios V, Matsakas A, Petridou A, Ring S, Sagredos A, Melissopoulou A, Tsigilis N, Nikolaidis M. Effect of supplementation with conjugated linoleic acid on human serum lipids and body fat. J Nutr Biochem. 2001. 12:585–594.

36. Munday JS, Thompson KG, James KA. Dietary conjugated linoleic acids promote fatty streak formation in the C57BL/6 mouse atherosclerosis model. Br J Nutr. 1999. 81:251–255.

37. Nestel P, Fujii A, Allen T. The cis-9,trans-11 isomer of conjugated linoleic acid (CLA) lowers plasma triglyceride and raises HDL cholesterol concentrations but does not suppress aortic atherosclerosis in diabetic apoE-deficient mice. Atherosclerosis. 2006. 189:282–287.

38. Nicolosi RJ, Rogers EJ, Kritchevsky D, Scimeca JA, Huth PJ. Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. Artery. 1997. 22:266–277.

39. Nugent AP, Roche HM, Noone EJ, Long A, Kelleher DK, Gibney MJ. The effects of conjugated linoleic acid supplementationon immune function in healthy volunteers. Eur J Clin Nutr. 2005. 59:742–750.

40. O'Hagan S, Menzel A. A subchronic 90-day oral rat toxicity study and in vitro genotoxicity studies with a conjugated linoleic acid product. Food Chem Toxicol. 2003. 41:1749–1760.

41. Olefsky JM. Nuclear receptor minireview series. J Biol Chem. 2001. 276:36863–36864.

42. Pariza MW. Perspective on the safety and effectiveness of conjugated linoleic acid. Am J Clin Nutr. 2004. 79:1132S–1136S.

43. Pariza MW, Ha YL. Conjugated dienoic derivatives of linoleic acid: a new class of anticarcinogens. Med Oncol Tumor Pharmacother. 1990. 7:169–171.

44. Pariza MW, Park Y, Cook ME. The biologically active isomers of conjugated linoleic acid. Prog Lipid Res. 2001. 40:283–298.

45. Petridou A, Mougios V, Sagredos A. Supplementation with CLA: isomer incorporation into serum lipids and effect on body fat of women. Lipids. 2003. 38:805–811.

46. Rahman MM, Bhattacharya A, Banu J, Fernandes G. Conjugated linoleic acid protects against age-associated bone loss in C57BL/6 female mice. J Nutr Biochem. 2007. 18:467–474.

47. Rainer L, Heiss CJ. Conjugated linoleic acid: health implications and effects on body composition. J Am Diet Assoc. 2004. 104:963–968.

48. Ramakers JD, Plat J, Sebedio JL, Mensink RP. Effects of the individual isomers cis-9,trans-11 vs. trans-10,cis-12 of conjugated linoleic acid (CLA) on inflammation parameters in moderately overweight subjects with LDL-phenotype B. Lipids. 2005. 40:909–918.

49. Ringseis R, Muller A, Herter C, Gahler S, Steinhart H, Eder K. CLA isomers inhibit TNFalpha-induced eicosanoid release from human vascular smooth muscle cells via a PPARgamma ligand-like action. Biochim Biophys Acta. 2006. 1760:290–300.

50. Ritzenthaler KL, McGuire MK, McGuire MA, Shultz TD, Koepp AE, Luedecke LO, Hanson TW, Dasgupta N, Chew BP. Consumption of conjugated linoleic acid (CLA) from CLA-enriched cheese does not alter milk fat or immunity in lactating women. J Nutr. 2005. 135:422–430.

51. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999. 340:115–126.

52. Schleser S, Ringseis R, Eder K. Conjugated linoleic acids have no effect on TNFalpha-induced adhesion molecule expression, U937 monocyte adhesion, and chemokine release in human aortic endothelial cells. Atherosclerosis. 2006. 186:337–344.

53. Scimeca JA. Toxicological evaluation of dietary conjugatedlinoleic acid in male Fischer 344 rats. Food Chem Toxicol. 1998. 36:391–395.

54. Sneddon AA, McLeod E, Wahle KW, Arthur JR. Cytokine-induced monocyte adhesion to endothelial cells involves platelet-activating factor: suppression by conjugated linoleic acid. Biochim Biophys Acta. 2006. 1761:793–801.

55. Song HJ, Grant I, Rotondo D, Mohede I, Sattar N, Heys SD, Wahle KW. Effect of CLA supplementation on immune function in young healthy volunteers. Eur J Clin Nutr. 2005. 59:508–517.

56. Sugano M, Tsujita A, Yamasaki M, Noguchi M, Yamada K. Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats. Lipids. 1998. 33:521–527.

57. Toomey S, Harhen B, Roche HM, Fitzgerald D, Belton O. Profound resolution of early atherosclerosis with conjugated linoleic acid. Atherosclerosis. 2006. 187:40–49.

58. Tricon S, Burdge GC, Kew S, Banerjee T, Russell JJ, Grimble RF, Williams CM, Calder PC, Yaqoob P. Effects of cis-9, trans-11 and trans-10,cis-12 conjugated linoleic acid on immune cell function in healthy humans. Am J Clin Nutr. 2004a. 80:1626–1633.

59. Tricon S, Burdge GC, Kew S, Banerjee T, Russell JJ, Jones EL, Grimble RF, Williams CM, Yaqoob P, Calder PC. Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans. Am J Clin Nutr. 2004b. 80:614–620.

60. Wahle KW, Heys SD, Rotondo D. Conjugated linoleic acids: are they beneficial or detrimental to health? Prog Lipid Res. 2004. 43:553–587.

61. Weldon S, Mitchell S, Kelleher D, Gibney MJ, Roche HM. Conjugated linoleic acid and atherosclerosis: no effect on molecular markers of cholesterol homeostasis in THP-1 macrophages. Atherosclerosis. 2004. 174:261–273.

62. Whigham LD, Cook ME, Atkinson RL. Conjugated linoleic acid: implications for human health. Pharmacol Res. 2000. 42:503–510.

63. Wilson TA, Nicolosi RJ, Saati A, Kotyla T, Kritchevsky D. Conjugated linoleic acid isomers reduce blood cholesterol levels but not aortic cholesterol accumulation in hypercholesterolemic hamsters. Lipids. 2006. 41:41–48.

64. Wong MW, Chew BP, Wong TS, Hosick HL, Boylston TD, Shultz TD. Effects of dietary conjugated linoleic acid on lymphocyte function and growth of mammary tumors in mice. Anticancer Res. 1997. 17:987–993.

65. Yasui Y, Suzuki R, Kohno H, Miyamoto S, Beppu F, Hosokawa M, Miyashita K, Tanaka T. 9trans,11trans conjugated linoleic acid inhibits the development of azoxymethane-induced colonic aberrant crypt foci in rats. Nutr Cancer. 2007. 59:82–91.

66. Yu Y, Correll PH, Vanden Heuvel JP. Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPAR gamma-dependent mechanism. Biochim Biophys Acta. 2002. 1581:89–99.

67. Yurawecz MP. Advances in conjugated linoleic acid research. 1999. Champaign, IL. USA: AOCS Press;154–179.

68. Zulet MA, Marti A, Parra MD, Martinez JA. Inflammation and conjugated linoleic acid: mechanisms of action and implications for human health. J Physiol Biochem. 2005. 61:483–494.