DOI QR코드

DOI QR Code

Beneficial Biological Activities of Conjugated Linoleic Acid

CLA의 생물학적 기능

  • 하영래 ((주)HK바이오텍, 부설 HK항노화연구소) ;
  • 김정옥 ((주)HK바이오텍, 부설 HK항노화연구소) ;
  • 김영숙 ((주)HK바이오텍, 부설 HK항노화연구소)
  • Received : 2017.08.11
  • Accepted : 2017.08.28
  • Published : 2017.08.30

Abstract

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid with conjugated double bonds at C9,C11 and C10,C12 positions. Of possible CLA isomers, a naturally occurring CLA isomer is c9,t11-CLA which is produced from linoleic acid by linoleate isomerase from various rumen and lactic bacteria, and mushroom mycelia. Meanwhile, synthetically prepared CLA contained an equal amount of c9,t11-CLA and t10,c12-CLA isomers, and other isomers as minor constituents. CLA was firstly mentioned in 1939 during the elaidinization reaction of linoleic acid. Thereafter, CLA was not an attractant to scientists because it was not scientifically interested any more. However, since the anticarcinogenic action was driven from 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis in 1987, CLA-related researches were drastically elevated, resulting in approximately 6,100 research papers in literature, so far. CLA exhibited the significant biological activities: anticarcinogenic, antidiabetic, antihypertensive, antiatherosclerotic, body-fat reducing, antioxidative, antiinflammatory, testosterone producing and other activities. Interestingly, two major CLA isomers, c9,t11-CLA and t10,c12-CLA, exhibited different biological activities. Meanwhile, t,t-CLA isomers which is minor constituent of chemically synthesized CLA from linoleic acid exhibited more potent anticarcinogenic activity in carcinogen-induced animal models and cancer cell lines than other CLA isomrs. In the present review, the significant biological activities of CLA were discussed along with historical studies of CLA since 1939.

Acknowledgement

Supported by : 경상남도, 중기청

References

  1. Ai, Y. M., Kadir, A. A., Ahmad, Z., Yaakub, H., Zmiruddin, Z. A. and Abdullah, M. N. H. 2012. Free radical scavenging activity of conjugated linoleic acid as single or mixed isomers. Pharm. Biol. 50, 712-719. https://doi.org/10.3109/13880209.2011.621714
  2. Arbones-Mainar, J. M., Navarro, M. A., Guzman, M. A., Arnal, C., Surra, J. C., Acin, S., Carnicer, R., Osada, J. and Roche, H. M. 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
  3. Barone, R., Macaluso, F., Catanese, P., Marino Gammazza, A., Rizzuto, L., Rizzuto, L., Marozzi, P., Giudice, G. L., Stampone, T., Cappello, F., Morici, G., Zummo, G., Farina, F. and Felice, V. D. 2013. Endurance exercise and conjugated linoleic acid (CLA) supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis. PLoS One 8, e79686. https://doi.org/10.1371/journal.pone.0079686
  4. Bassaganya-Riera, J. and Hontecillas, R. 2006. CLA and n-3 PUFA differentially modulate clinical activity and colonic PPAR-responsive gene expression in a pig model of experimental IBD. Clin. Nutr. 25, 454-465. https://doi.org/10.1016/j.clnu.2005.12.008
  5. Bassaganya-Riera, J., Reynolds, K., Martino-Catt, S., Cui, Y., Hennighausen, L., Gonzalez, F., Rohrer, J., Benninghoff, A. U. and Hontecillas, R. 2004. Activation of $PPAR{\gamma}$ and ${\delta}$ by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterology 127, 777-791. https://doi.org/10.1053/j.gastro.2004.06.049
  6. Benjamin, S., Prakasan, P., Sreedharan, S., Wright, A. D. G. and Spener, F. 2015. Pros and cons of CLA consumption: an insight from clinical evidences. Nutr. Meta. 12, 1-20. https://doi.org/10.1186/1743-7075-12-1
  7. Bruen, R., Fitzsimons, S. and Belton, O. 2017. Atheroprotective effects of conjugated linoleic acid. Br. J. Clin. Pharmacol. 83, 46-53. https://doi.org/10.1111/bcp.12948
  8. Chen, Z. Y., Chan, P. T., Kwan, K. Y. and Zhang, A. 1997. Reassessment of the antioxidant activity of conjugated linoleic acids. J. Amer. Oil Chem. Soc. 74, 749-753. https://doi.org/10.1007/s11746-997-0213-y
  9. Chao, P. M., Chen, W. H., Liao, C. H. and Shaw, H. M. 2010. Conjugated linoleic acid causes a marked increase in liver ${\alpha}$-tocopherol and liver ${\alpha}$-tocopherol transfer protein in C57BL/6 J Mice. Int. J. Vitam. Nutr. Res. 80, 65-73. https://doi.org/10.1024/0300-9831/a000007
  10. Forbes, W. C. and Neville, H. A. 1940. Wijs iodine numbers for conjugated double bonds: influence of sample-Reagent Ratio. Ind. Eng. Chem. Anal. Ed. 12, 72-74. https://doi.org/10.1021/ac50142a003
  11. Gaullier, J. M., Halse, J., Hoye, K., Kristiansen, K., Fagertun, H., Vik, H. and 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
  12. Ha, Y. L., Grimm, N. K. and Pariza, M. W. 1987. Anticarcinogens from fried ground beef: Heat-altered derivatives of linoleic acid. Carcinogenesis 8, 1881-1887. https://doi.org/10.1093/carcin/8.12.1881
  13. Ha, Y. L., Grimm, N. K. and Pariza, M. W. 1989. Newly recognized anticarcinogenic fatty acids: Identification and quantification in natural and processed cheeses. J. Agric. Food Chem. 37, 75-81. https://doi.org/10.1021/jf00085a018
  14. 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.
  15. Hontecillas, R. and Bassaganya-Riera, J. 2007. Peroxisome proliferator-activated receptor ${\gamma}$ is required for regulatory CD4+ T cell-mediated protection against colitis. J. Immunol. 178, 2940-2949. https://doi.org/10.4049/jimmunol.178.5.2940
  16. Houseknecht, K. L., Heuvel, J. P. V., Moya-Camarena, S. Y., Portocarrero, C. P., Peck, L. W., Nickel, K. P. and Belury, M. A. 1998. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/ fa rat. BBRC 244, 678-682.
  17. Hughes, P. E., Hunter, W. J. and Tove, S. B. 1982. Biohydrogenation of unsaturated fatty acids. Purification and properties of cis-9,trans-11-octadecadienoate reductase. J. Biol. Chem. 257, 3643-3649.
  18. Hunter, W. J., Baker, F. C., Rosenfeld, I. S., Keyser, J. B. and Tove, S. B. 1976. Biohydrogenation of unsaturated fatty acids. Hydrogenation by cell free preparations of Butyrivibrio fibrisolvens. J. Biol. Chem. 251, 2241-2247.
  19. Inoue, N., Nagao, K., Hirata, I., Wang, Y.-M. and Yanagita, T. 2004. Conjugated linoleic acid prevents the development of essential hypertension in spontaneously hypertensive rats. BBRC 323, 679-684.
  20. Ip, C. and Pariza, M. W. 1991. Mammary cancer prevention by conjugated dienoic derivative of linoleic acid. Cancer Res. 51, 6118-6124.
  21. Ip, C., Scimeca, J. A. and Thompson, H. J. 1994. Conjugated linoleic acid. Cancer 74, 1050-1054. https://doi.org/10.1002/1097-0142(19940801)74:3+<1050::AID-CNCR2820741512>3.0.CO;2-I
  22. Islam, M. A., Kim, Y. S., Oh, T. W., Kim, G. S., Won, C. K., Kim, H. G., Choi, M. S., Kim, J. O. and Ha, Y. L. 2010. Superior anticarcinogenic activity of trans, trans-conjugated linoleic acid in N-methyl-N-nitrosourea-induced rat mammary tumorigenesis. J. Agric. Food Chem. 58, 5670-5678. https://doi.org/10.1021/jf100117a
  23. Jiang, W., Nie, S., Qu, Z., Bi, C. and Shan, A. 2014. The effects of conjugated linoleic acid on growth performance, carcass traits, meat quality, antioxidant capacity, and fatty acid composition of broilers fed corn dried distillers grains with solubles. Poult. Sci. 93, 1202-1210. https://doi.org/10.3382/ps.2013-03683
  24. Kass, J. P. and Burr, G. O. 1939. The elaidinization of linoleic acid. J. Am. Chem. Soc. 61, 1062-1066. https://doi.org/10.1021/ja01874a022
  25. Kepler, C. R., Hirons, K. P., McNeill, J. J. and Tove, S. B. 1966. Intermediates and products of the biohydrogenation of linoleic acid by Butyrinvibrio fibrisolvens. J. Biol. Chem. 241, 1350-1354.
  26. Kepler, C. R. and Tove, S. B. 1967. Biohydrogenation of unsaturated fatty acids. 3. Purification and properties of a linoleate delta-12-cis, delta-11-trans-isomerase from Butyrivibrio fibrisolvens. J. Biol. Chem. 242, 5686-5692.
  27. Kim, J. H., Kim, O. H., Ha, Y. L. and Kim, J. O. 2008. Supplementation of conjugated linoleic acid with gamma-oryzanol for 12 weeks effectively reduces body fat in healthy overweight Korean women. J. Food Sci. Nutr. 13, 146-156.
  28. Lee. K. N., Kritchevsky, D. and Parizaa, M. W. 1994. Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 108, 19-25. https://doi.org/10.1016/0021-9150(94)90034-5
  29. MacAluso, F., Morici, G., Catanese, P., Farina, F. and Di Felice, V. 2012. Effect of conjugated linoleic acid on testosterone levels in vitro and in vivo after an acute bout of resistance exercise. J. Strength Cond. Res. 26, 1667-1674. https://doi.org/10.1519/JSC.0b013e318231ab78
  30. Maczulak, A. E., Dehority, B. A. and Palmquist, D. L. 1981. Effects of long-chain fatty acids on growth of rumen bacteria. Appl. Environ. Microbiol. 42, 856-862.
  31. Mitchell, J. H. and Kraybill, H. R. 1942. Formation of conjugated material during bleaching of vegetable oils. J. Am. Chem. Soc. 64, 988-994. https://doi.org/10.1021/ja01256a069
  32. Moloney, F., Yeow, T. P., Mullen, A., Nolan, J. J. and Roche, H. M. 2004. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am. J. Clin. Nutr. 80, 887-895. https://doi.org/10.1093/ajcn/80.4.887
  33. Nagao, K., Inoue, N., Wang, Y. M. and Yanagita, T. 2003. Conjugated linoleic acid enhances plasma adiponectin level and alleviates hyperinsulinemia and hypertension in Zucker diabetic fatty (fa/fa) rats. BBRC 310, 562-566.
  34. Nagao, K., Inoue, N., Wang, Y. M., Hirata, J., Shimada, Y., Nagao, T., Matsui, T. and Yanagita, T. 2003. The 10trans, 12cis isomer of conjugated linoleic acid suppresses the development of hypertension in Otsuka Long-Evans Tokushima fatty rats. BBRC 306, 134-138.
  35. Nakamura, Y. K. and Omaye, S. T. 2009. Conjugated linoleic acid isomers' roles in the regulation of PPAR-${\gamma}$ and NF-${\kappa}B$ DNA binding and subsequent expression of antioxidant enzymes in human umbilical vein endothelial cells. Nutrition 25, 800-811. https://doi.org/10.1016/j.nut.2009.01.003
  36. Nichols, P. L., Herb, S. F. and Riemenschneider, R. W. 1951. Isomers of conjugated fatty Acids. I. alkali-isomerized linoleic Acid. J. Am. Chem. Soc. 73, 247-252. https://doi.org/10.1021/ja01145a084
  37. Pariza, M. W., Park, Y. and Cook, M. E. 2000. Mechanisms of action of conjugated linoleic acid: evidence and speculation. Proc. Soc. Exp. Biol. Med. 223, 8-13. https://doi.org/10.1046/j.1525-1373.2000.22302.x
  38. 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. https://doi.org/10.1007/s11745-997-0109-x
  39. Park, Y., Ha, Y. L. and Pariza, M. W. 2007. ${\pi}$-Complex formation of conjugated linoleic acid with iron. Food Chem. 100, 972-976. https://doi.org/10.1016/j.foodchem.2005.11.006
  40. 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. https://doi.org/10.1007/s11745-999-0358-8
  41. Rakib, M. A., Lee, W. S., Kim, G. S., Han, J. H., Kim, J. O. and Ha, Y. L. 2013. Antiproliferative action of conjugated linoleic acid on human MCF-7 breast cancer cells mediated by enhancement of gap junctional intercellular communication through inactivation of NF-${\kappa}B$. Evid. Based Complement. Alternat. Med. 2013, 429393.
  42. Rakib, M. A., Kim, Y. S., Jang, W. J., Jang, J. S. Kang, S. J. and Ha, Y. L. 2011. Preventive effect of t,t-conjugated linoleic acid on 12-O- tetradecanoylphorbol-13-acetate-induced inhibition of gap junctional intercellular communication in human mammary epithelial MCF-10A cells. J. Agric. Food Chem. 59, 4164-4170. https://doi.org/10.1021/jf1046909
  43. Polan, C. E., McNeil, J. J. and Tove, S. B. 1964. Biohydrogenation of unsaturated fatty acids by rumen bacteria. J. Bacteriol. 88, 1056-1064.
  44. Riserus, 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 the metabolic syndrome. Diabetes Care 25, 1516-1521. https://doi.org/10.2337/diacare.25.9.1516
  45. Reiser, R. 1950. Conjugated linoleic acid in rat tissue lipids after ingestion as free acid and as triglyceride. Proc. Soc. Exp. Biol. Med. 74, 666-669. https://doi.org/10.3181/00379727-74-18009
  46. Ryder, J. W., Portocarrero, C. P., Song, X. M., Cui, L., Yu, M., Combatsiaris, T., Galuska, D., Bauman, D. E., Barbano, D. M., Charron, M. J., Zierath, J. R. and Houseknecht, K. L. 2001. Isomer-specific antidiabetic properties of conjugated linoleic acid. Diabetes 50, 1149-1157 https://doi.org/10.2337/diabetes.50.5.1149
  47. Svechnikov, K., Spatafora, C., Svechnikova, I., Tringali, C., and Soder, O. 2009. Effects of resveratrol analogs on steroidogenesis and mitochondrial function in rat Leydig cells in vitro. J. Appl. Toxicol. 29, 673-80. https://doi.org/10.1002/jat.1456
  48. Thom, E., Wadstein, J. and Gudmundsen, O. 2001. Conjugated linoleic acid reduces body fat in healthy exercising humans. J. Int. Med. Res. 29, 392-396. https://doi.org/10.1177/147323000102900503
  49. Toomey, S., Harhen, B., Roche, H. M., Fitzgerald, D. and 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
  50. von Mikusch, J. D. and Frazier, C. 1941. Woburn iodine absorption method: A measure of total unsaturation in the presence of conjugated double bonds. Ind. Eng. Chem. Anal. Ed. 13, 782-789. https://doi.org/10.1021/i560099a009
  51. von Mikusch, J. D. 1942. Solid 10,12-octadecadienoic Acid-1. A new conjugated linoleic acid melting at $57^{\circ}$. J. Am. Chem. Soc. 64, 1580-1582. https://doi.org/10.1021/ja01259a025
  52. von Soosten, D., Meyer, U., Piechotta, M., Flachowsky, G. and Danicke, S. 2012. Effect of conjugated linoleic acid supplementation on body composition, body fat mobilization, protein accretion and energy utilization in early lactataion dairy cows. J. Dairy Sci. 95, 1222-1239. https://doi.org/10.3168/jds.2011-4548
  53. Wang, M. P., Choi, T. W., Kang, B. T. and Kang, J. H. 2015. Effect of trans-10, cis-12 Conjugated linoleic acid on calcium-dependent reactive oxygen species and nitric oxide production and nuclear ractor-${\kappa}B$ activation in lipopolysaccharide-stimulated RAW 264.7 Cells. Kor. Clin. Vet. 32, 135-140. https://doi.org/10.17555/jvc.2015.04.32.2.135
  54. Weisser, J., Landreh, L., Soder, O. and Svechnikov, K. 2011. Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells. Mol. Cell. Endocrinol. 341, 18-24. https://doi.org/10.1016/j.mce.2011.03.008
  55. Yang, J., Wang, H. P., Zhou, L. M., Zhou, L., Chen, T. and Qin, L. Q. 2015. Effect of conjugated linoleic acid on blood pressure: a meta-analysis of randomized, double-blind placebo-controlled trials. Lipids Health. Dis. 14, 11. https://doi.org/10.1186/s12944-015-0010-9
  56. Yu, L., Adams, W. and Gabel, M. 2002. Conjugated linoleic acid isomers differ in their free radical scavenging properties. J. Agric. Food Chem. 50, 4135-4140. https://doi.org/10.1021/jf020086a
  57. Zhao, W. S., Zhai, J. J., Wang, Y. H., Xie, P. S., Yin, X. J., Li, L. X. and Cheng, K. L. 2009. Conjugated linoleic acid supplementation enhances antihypertensive effect of ramipril in Chinese patients with obesity-related hypertension. Am. J. Hypertens. 22, 680-686. https://doi.org/10.1038/ajh.2009.56
  58. Zuo, R., Ai, Q., Mai, K. and Xu, W. 2013. Effects of conjugated linoleic acid on growth, non-specific immunity, antioxidant capacity, lipid deposition and related gene expression in juvenile large yellow croaker (Larmichthys crocea) fed soyabean oil-based diets. Br. J. Nutr. 110, 1220-1232. https://doi.org/10.1017/S0007114513000378