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

  • Lee, Yun-Kyoung
  • Published : 2008.12.31

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.

Keywords

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

References

  1. Albers R, van der Wielen RP, Brink EJ, Hendriks HF, Dorovska- Taran VN & Mohede IC (2003). 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 57:595-603 https://doi.org/10.1038/sj.ejcn.1601585
  2. Benito P, Nelson GJ, Kelley DS, Bartolini G, Schmidt PC & Simon V (2001). The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids 36:229-236 https://doi.org/10.1007/s11745-001-0712-x
  3. Bhattacharya A, Banu J, Rahman M, Causey J & Fernandes G (2006). Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem 17:789-810 https://doi.org/10.1016/j.jnutbio.2006.02.009
  4. Coen P, Cummins P, Birney Y, Devery R & Cahill P (2004). Modulation of nitric oxide and 6-keto-prostaglandin F(1alpha) production in bovine aortic endothelial cells by conjugated linoleic acid. Endothelium 11:211-220 https://doi.org/10.1080/10623320490512435
  5. 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 (2004). Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-gamma, reduces acute inflammation. Eur J Pharmacol 483:79-93 https://doi.org/10.1016/j.ejphar.2003.10.056
  6. Evans M, Brown J & McIntosh M (2002). Isomer-specific effects of conjugated linoleic acid (CLA) on adiposity and lipid metabolism. J Nutr Biochem 13:508 https://doi.org/10.1016/S0955-2863(02)00211-5
  7. Kishino S, Ogawa J, Ando A, Iwashita T, Fujita T, Kawashima H & Shimizu S (2003). Structural analysis of conjugated linoleic acid produced by Lactobacillus plantarum, and factors affecting isomer production. Biosci Biotechnol Biochem 67:179-182 https://doi.org/10.1271/bbb.67.179
  8. Lee Y, Thompson JT, de Lera AR & Vanden Heuvel JP (2008). Isomerspecific effects of conjugated linoleic acid on gene expression in RAW 264.7. J Nutr Biochem 5:[Epub ahead of print]
  9. O'Hagan S & Menzel A (2003). A subchronic 90-day oral rat toxicity study and in vitro genotoxicity studies with a conjugated linoleic acid product. Food Chem Toxicol 41:1749-1760 https://doi.org/10.1016/S0278-6915(03)00203-5
  10. Pariza MW & Ha YL (1990). Conjugated dienoic derivatives of linoleic acid: a new class of anticarcinogens. Med Oncol Tumor Pharmacother 7:169-171
  11. Pariza MW, Park Y & Cook ME (2001). The biologically active isomers of conjugated linoleic acid. Prog Lipid Res 40:283-298 https://doi.org/10.1016/S0163-7827(01)00008-X
  12. Rahman MM, Bhattacharya A, Banu J & Fernandes G (2007). Conjugated linoleic acid protects against age-associated bone loss in C57BL/6 female mice. J Nutr Biochem 18:467-474 https://doi.org/10.1016/j.jnutbio.2006.08.002
  13. Ramakers JD, Plat J, Sebedio JL & Mensink RP (2005). 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 40:909-918 https://doi.org/10.1007/s11745-005-1451-8
  14. Wilson TA, Nicolosi RJ, Saati A, Kotyla T & Kritchevsky D (2006). Conjugated linoleic acid isomers reduce blood cholesterol levels but not aortic cholesterol accumulation in hypercholesterolemic hamsters. Lipids 41:41-48 https://doi.org/10.1007/s11745-006-5068-8
  15. Wong MW, Chew BP, Wong TS, Hosick HL, Boylston TD & Shultz TD (1997). Effects of dietary conjugated linoleic acid on lymphocyte function and growth of mammary tumors in mice. Anticancer Res 17:987-993
  16. Yu Y, Correll PH & Vanden Heuvel JP (2002). Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPAR gamma-dependent mechanism. Biochim Biophys Acta 1581:89-99 https://doi.org/10.1016/S1388-1981(02)00126-9
  17. Cheng WL, Lii CK, Chen HW, Lin TH & Liu KL (2004). Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-kappaB pathway. J Agric Food Chem 52:71-78 https://doi.org/10.1021/jf0348626
  18. Rainer L & Heiss CJ (2004). Conjugated linoleic acid: health implications and effects on body composition. J Am Diet Assoc 104:963-968 https://doi.org/10.1016/j.jada.2004.03.016
  19. Calder PC & Grimble RF (2002). Polyunsaturated fatty acids, inflammation and immunity. Eur J Clin Nutr 56:S14-S19 https://doi.org/10.1038/sj.ejcn.1601478
  20. Nugent AP, Roche HM, Noone EJ, Long A, Kelleher DK & Gibney MJ (2005). The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers. Eur J Clin Nutr 59:742-750 https://doi.org/10.1038/sj.ejcn.1602132
  21. Petridou A, Mougios V & Sagredos A (2003). Supplementation with CLA: isomer incorporation into serum lipids and effect on body fat of women. Lipids 38:805-811 https://doi.org/10.1007/s11745-003-1129-2
  22. Zulet MA, Marti A, Parra MD & Martinez JA (2005). Inflammation and conjugated linoleic acid: mechanisms of action and implications for human health. J Physiol Biochem 61:483-494 https://doi.org/10.1007/BF03168454
  23. Mougios V, Matsakas A, Petridou A, Ring S, Sagredos A, Melissopoulou A, Tsigilis N & Nikolaidis M (2001). Effect of supplementation with conjugated linoleic acid on human serum lipids and body fat. J Nutr Biochem 12:585-594 https://doi.org/10.1016/S0955-2863(01)00177-2
  24. Kramer JK, Parodi PW, Jensen RG, Mossoba MM, Yurawecz MP & Adlof RO (1998). Rumenic acid: a proposed common name for the major conjugated linoleic acid isomer found in natural products. Lipids 33:835 https://doi.org/10.1007/s11745-998-0279-6
  25. Ross R (1999). Atherosclerosis--an inflammatory disease. N Engl J Med 340:115-126 https://doi.org/10.1056/NEJM199901143400207
  26. Whigham LD, Cook ME & Atkinson RL (2000). Conjugated linoleic acid: implications for human health. Pharmacol Res 42:503-510 https://doi.org/10.1006/phrs.2000.0735
  27. Nicolosi RJ, Rogers EJ, Kritchevsky D, Scimeca JA & Huth PJ (1997). Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. Artery 22:266-277
  28. Pariza MW (2004). Perspective on the safety and effectiveness of conjugated linoleic acid. Am J Clin Nutr 79:1132S-1136S https://doi.org/10.1093/ajcn/79.6.1132S
  29. Kelly GS (2001). Conjugated linoleic acid: a review. Altern Med Rev 6:367-382
  30. Ecker J, Langmann T, Moehle C & Schmitz G (2007). Isomer specific effects of Conjugated Linoleic Acid on macrophage ABCG1 transcription by a SREBP-1c dependent mechanism. Biochem Biophys Res Commun 352:805-811 https://doi.org/10.1016/j.bbrc.2006.11.087
  31. Kritchevsky D, Tepper SA, Wright S, Tso P & Czarnecki SK (2000). Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits. J Am Coll Nutr 19:472S-477S https://doi.org/10.1080/07315724.2000.10718950
  32. Kelley DS, Taylor PC, Rudolph IL, Benito P, Nelson GJ, Mackey BE & Erickson KL (2000). Dietary conjugated linoleic acid did not alter immune status in young healthy women. Lipids 35:1065-1071 https://doi.org/10.1007/s11745-000-0620-0
  33. Schleser S, Ringseis R & Eder K (2006). Conjugated linoleic acids have no effect on TNFalpha-induced adhesion molecule expression, U937 monocyte adhesion, and chemokine release in human aortic endothelial cells. Atherosclerosis 186:337-344 https://doi.org/10.1016/j.atherosclerosis.2005.08.018
  34. Kelley DS, Warren JM, Simon VA, Bartolini G, Mackey BE & Erickson KL (2002). Similar effects of c9,t11-CLA and t10, c12-CLA on immune cell functions in mice. Lipids 37:725-728 https://doi.org/10.1007/s11745-002-0954-7
  35. Arbones-Mainar JM, Navarro MA, Guzman MA, Arnal C, Surra JC, Acin S, Carnicer R, Osada J & Roche HM (2006). Selective effect of conjugated linoleic acid isomers on atherosclerotic lesion development in apolipoprotein E knockout mice. Atherosclerosis 189:318-327 https://doi.org/10.1016/j.atherosclerosis.2006.01.015
  36. Yurawecz MP (1999). Advances in conjugated linoleic acid research. Champaign, Ill.: AOCS Press. p.154-179. Champaign, IL. USA
  37. Sneddon AA, McLeod E, Wahle KW & Arthur JR (2006). Cytokineinduced monocyte adhesion to endothelial cells involves plateletactivating factor: suppression by conjugated linoleic acid. Biochim Biophys Acta 1761:793-801 https://doi.org/10.1016/j.bbalip.2006.05.014
  38. Desroches S, Chouinard PY, Galibois I, Corneau L, Delisle J, Lamarche B, Couture P & Bergeron N (2005). 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 82:309-319 https://doi.org/10.1093/ajcn/82.2.309
  39. Kishino S, Ogawa J, Ando A, Omura Y & Shimizu S (2002). Ricinoleic acid and castor oil as substrates for conjugated linoleic acid production by washed cells of Lactobacillus plantarum. Biosci Biotechnol Biochem 66:2283-2286 https://doi.org/10.1271/bbb.66.2283
  40. Song HJ, Grant I, Rotondo D, Mohede I, Sattar N, Heys SD & Wahle KW (2005). Effect of CLA supplementation on immune function in young healthy volunteers. Eur J Clin Nutr 59:508-517 https://doi.org/10.1038/sj.ejcn.1602102
  41. Tricon S, Burdge GC, Kew S, Banerjee T, Russell JJ, Grimble RF, Williams CM, Calder PC & Yaqoob P (2004a). 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 80:1626-1633 https://doi.org/10.1093/ajcn/80.6.1626
  42. Yasui Y, Suzuki R, Kohno H, Miyamoto S, Beppu F, Hosokawa M, Miyashita K & Tanaka T (2007). 9trans,11trans conjugated linoleic acid inhibits the development of azoxymethane-induced colonic aberrant crypt foci in rats. Nutr Cancer 59:82-91 https://doi.org/10.1080/01635580701419055
  43. Cook ME, Miller CC, Park Y & Pariza M (1993). Immune modulation by altered nutrient metabolism: nutritional control of immune-induced growth depression. Poult Sci 72:1301-1305 https://doi.org/10.3382/ps.0721301
  44. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H & Gudmundsen O (2004). Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am J Clin Nutr 79:1118-1125 https://doi.org/10.1093/ajcn/79.6.1118
  45. Jaudszus A, Foerster M, Kroegel C, Wolf I & Jahreis G (2005). 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 1737:111-1118 https://doi.org/10.1016/j.bbalip.2005.11.001
  46. Munday JS, Thompson KG & James KA (1999). Dietary conjugated linoleic acids promote fatty streak formation in the C57BL/6 mouse atherosclerosis model. Br J Nutr 81:251-255 https://doi.org/10.1017/S0007114599000458
  47. Wahle KW, Heys SD & Rotondo D (2004). Conjugated linoleic acids: are they beneficial or detrimental to health? Prog Lipid Res 43: 553-587 https://doi.org/10.1016/j.plipres.2004.08.002
  48. Gaullier JM, Berven G, Blankson H & Gudmundsen O (2002). Clinical trial results support a preference for using CLA preparations enriched with two isomers rather than four isomers in human studies. Lipids 37:1019-1025 https://doi.org/10.1007/s11745-002-0995-y
  49. Lee KN, Kritchevsky D & Pariza MW (1994). Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 108:19-25 https://doi.org/10.1016/0021-9150(94)90034-5
  50. Li Y & Watkins BA (1998). 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 33:417-425 https://doi.org/10.1007/s11745-998-0223-9
  51. Nestel P, Fujii A & Allen T (2006). 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 189:282-287 https://doi.org/10.1016/j.atherosclerosis.2005.12.020
  52. Ritzenthaler KL, McGuire MK, McGuire MA, Shultz TD, Koepp AE, Luedecke LO, Hanson TW, Dasgupta N & Chew BP (2005). Consumption of conjugated linoleic acid (CLA) from CLA-enriched cheese does not alter milk fat or immunity in lactating women. J Nutr 135:422-430
  53. Tricon S, Burdge GC, Kew S, Banerjee T, Russell JJ, Jones EL, Grimble RF, Williams CM, Yaqoob P & Calder PC (2004b). 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 80:614-620 https://doi.org/10.1093/ajcn/80.3.614
  54. Al-Madaney MM, Kramer JK, Deng Z & Vanderhoek JY (2003). Effects of lipid-esterified conjugated linoleic acid isomers on platelet function: evidence for stimulation of platelet phospholipase activity. Biochim Biophys Acta 1635:75-82 https://doi.org/10.1016/j.bbalip.2003.10.008
  55. Hayek MG, Han SN, Wu D, Watkins BA, Meydani M, Dorsey JL, Smith DE & Meydani SN (1999). Dietary conjugated linoleic acid influences the immune response of young and old C57BL/6NCrlBR mice. J Nutr 129:32-38
  56. Mitchell PL, Langille MA, Currie DL & McLeod RS (2005). Effect of conjugated linoleic acid isomers on lipoproteins and atherosclerosis in the Syrian Golden hamster. Biochim Biophys Acta 1734:269-276 https://doi.org/10.1016/j.bbalip.2005.04.007
  57. Ringseis R, Muller A, Herter C, Gahler S, Steinhart H & Eder K (2006). CLA isomers inhibit TNFalpha-induced eicosanoid release from human vascular smooth muscle cells via a PPARgamma ligand-like action. Biochim Biophys Acta 1760:290-300 https://doi.org/10.1016/j.bbagen.2005.12.002
  58. Scimeca JA (1998). Toxicological evaluation of dietary conjugated linoleic acid in male Fischer 344 rats. Food Chem Toxicol 36:391-395 https://doi.org/10.1016/S0278-6915(97)00169-5
  59. Beppu F, Hosokawa M, Tanaka L, Kohno H, Tanaka T & Miyashita K (2006). Potent inhibitory effect of trans9, trans11 isomer of conjugated linoleic acid on the growth of human colon cancer cells. J Nutr Biochem 17:830-836 https://doi.org/10.1016/j.jnutbio.2006.01.007
  60. Lai KL, Torres-Duarte AP & Vanderhoek JY (2005). 9-trans, 11-trans-CLA: antiproliferative and proapoptotic effects on bovine endothelial cells. Lipids 40:1107-1116 https://doi.org/10.1007/s11745-005-1474-1
  61. Toomey S, Harhen B, Roche HM, Fitzgerald D & Belton O (2006). Profound resolution of early atherosclerosis with conjugated linoleic acid. Atherosclerosis 187:40-49 https://doi.org/10.1016/j.atherosclerosis.2005.08.024
  62. Weldon S, Mitchell S, Kelleher D, Gibney MJ & Roche HM (2004). Conjugated linoleic acid and atherosclerosis: no effect on molecular markers of cholesterol homeostasis in THP-1 macrophages. Atherosclerosis 174:261-273 https://doi.org/10.1016/j.atherosclerosis.2004.02.007
  63. Olefsky JM (2001). Nuclear receptor minireview series. J Biol Chem 276:36863-36864 https://doi.org/10.1074/jbc.R100047200
  64. Sugano M, Tsujita A, Yamasaki M, Noguchi M & Yamada K (1998). Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats. Lipids 33:521-527 https://doi.org/10.1007/s11745-998-0236-4
  65. Ip C, Scimeca JA & Thompson HJ (1994). Conjugated linoleic acid. A powerful anticarcinogen from animal fat sources. Cancer 74:1050-1054 https://doi.org/10.1002/1097-0142(19940801)74:3+<1050::AID-CNCR2820741512>3.0.CO;2-I
  66. Luongo D, Bergamo P & Rossi M (2003). Effects of conjugated linoleic acid on growth and cytokine expression in Jurkat T cells. Immunol Lett 90:195-201 https://doi.org/10.1016/j.imlet.2003.09.012
  67. Huang YC, Luedecke LO & Shultz TD (1994). Effect of cheddar cheese consumption on plasma conjugated linoleic acid concentrations in men. Nutr Res 14:373-386 https://doi.org/10.1016/S0271-5317(05)80176-9
  68. Loscher CE, Draper E, Leavy O, Kelleher D, Mills KH & Roche HM (2005). Conjugated linoleic acid suppresses NF-kappa B activation and IL-12 production in dendritic cells through ERK-mediated IL-10 induction. J Immunol 175:4990-4998 https://doi.org/10.4049/jimmunol.175.8.4990