Effects of Conjugated Linoleic Acid and Stearic Acid on Apoptosis of the INS-1 β-cells and Pancreatic Islets Isolated from Zucker Obese (fa/fa) Rats

  • Jang, I.S. (Department of Animal Science & Biotechnology, RAIRC, Jinju National University) ;
  • Hwang, D.Y. (Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA) ;
  • Lee, J.E. (Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA) ;
  • Kim, Y.K. (Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA) ;
  • Kang, T.S. (Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA) ;
  • Hwang, J.H. (Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA) ;
  • Lim, C.H. ;
  • Chae, K.R. (Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA) ;
  • Jeong, J.H. (Department of Hotel Culinary Arts, Ansan College of Technology) ;
  • Cho, J.S. (Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA)
  • Received : 2002.10.09
  • Accepted : 2003.04.23
  • Published : 2003.07.01


To determine whether dietary fatty acids affect pancreatic $\beta$-cell function, the INS-1 $\beta$-cells and the pancreatic islets isolated from Zucker obese (fa/fa) rats were cultured with stearic acid and conjugated linoleic acid (CLA). As a result, DNA fragmentation laddering was substantially decreased in the INS-1 $\beta$-cells and the isolated pancreatic islets cultured with 2 mM CLA compared to those cultured with stearic acid. To investigate the mechanism by which CLA alleviates cell apoptosis under DNA fragmentation assay, we examined mRNA expressions of apoptosis-related proteins including Bax and Bcl-2 associated with cell death agonist and antagonist, respectively, in both INS-1 cells and islets cultured with 2 mM fatty acids. Bax mRNA expression was not altered by either stearic acid or CLA, whereas Bcl-2 mRNA expression was enhanced by CLA when compared to the stearic acid cultures. However, there were no changes in cell apoptosis and apoptotic-regulating gene products in either INS-1 cells or isolated islets treated with or without 2 mM CLA. It is concluded that CLA maintains $\beta$-cell viability via increased Bcl-2 expression compared to the stearic acid cultures, which may help to alleviate, at least somewhat, the onset of NIDDM in the physiological status. More detailed study is still needed to elucidate the effect of CLA on the prevention of fatty acid-induced $\beta$-cell apoptosis.


  1. Dunshea F. R., E. Ostrowska, B. Luxford, R. J. Smits, R. G. Campbell, D. N. D'Souza and B. P. Mullan. 2002. Dietary CLA Can decrease backfat in pigs hused under commercial conditions. Asian-Aust. J. Anim. Sci. 15(7):1011-1017.
  2. Maedler, K., G. A. Spinas, D. Dyntar, W. Moritz, N. Kaiser and M. Y. Donath. 2001. Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function. Diabetes 50:69-76.
  3. McCarthy, M. F. 2000. Toward practical prevention type II diabetes. Med. Hypotheses 54:786-793.
  4. Milburn, J. L., H. Hiroshi, Y. H. Lee, Y. Nagasawa, A. Ogawa, M. Ohneda, H. Beltrandel Rio, C. B. Newgard, J. H. Johnson and R. H. Unger. 1995. Pancreatic $\beta$-cells in obesity. J. Biol. Chem. 270:1295-1299.
  5. Shimabukuro, M., M. Wang, Y. Zhou, C. Newgard and R. H. Unger. 1998a. Protection against lipoapoptosis of $\beta$-cells through leptin-dependent maintenance of Bcl-2 expression. Proc. Natl. Acad. Sci. 95:9558-9561.
  6. Shimabukuro, M., Y. Zhou, M. Levi and R. H. Unger. 1998b. Fatty acid-induced $\beta$-cell apoptosis: A link between obesity and diabetes. Proc. Natl. Acad. Sci. 95:2498-2502.
  7. Wang, J. H., M. K. Song and M. B. Chang. 2002. Effect of concentrate level on the formation of CLA and transoctadecenoic acid by ruminal bacteria when incubated with oilseeds in vitro Asian-Aust. J. Anim. Sci. 15(5):687-694.
  8. Cnop, M., J. C. Hannaert, A. Hoorens, D. L. Eizirik and D. G. Pipeleers. 2001. Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 50:1771-1777.
  9. Campani, D., I. Esposito, U. Boggi, D. Cecchetti, M. Menicagli, F. De Negri, L. Colizzi, M. D. Chiaro, F. Mosca, G. Fornaciari and G. Bevilacqua. 2001. Bcl-2 expression in pancreas development and pancreatic cancer progression. J. Pathology 194:444-450.
  10. Dugan, M. E. R., J. L. Aalhus, A. L. Schaefer and J. K. G. Kramer. 1997. The effect of conjugated linoleic acid on fat to lean repartitioning and feed conversion in pigs. Can. J. Anim. Sci. 77:723-725.
  11. Cattan, P., T. Berney, S. Schena, D. Moland, A. Pileggi, C. Vizzardelli, C. Ricordi and L. Inverardi. 2001. Early assessment of apoptosis in isolated islets of langerhans. Transplantation 71:857-862.
  12. DeLany, J. P., F. Blohm, A. A. Truett, J. A. Scimeca and D. B. West. 1999. Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Am. J. Physiol. 276:R1172-1179.
  13. Park, Y., J. M. Storkson, K. J. Albright, W. Liu and M. W. Pariza. 1999. Evidence that the trans-10, cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 34:235-241.
  14. Shimabukuro, M., M. Ohneda, Y. Lee and R. H. Unger. 1997. Role of nitric oxide in obesity-induced $\beta$-cell disease. J. Clin. Invest. 100:290-295.
  15. Roche, E., I. Maestre, F. Martin, E. Fuentes, J. Casero, J. A. Reig and B. Soria. 2000. Nutrient toxicity in pancreatic beta-cell dysfunction. J. Physiol. Biochem. 56:119-128
  16. Zhou, Y., M. Shimabukro, M. Wang, Y. Lee, M. Higa, J. L. Milburn, C. B. Newgard and R. H. Unger. 1998. Role of peroxisome proliferator-activated receptor $\alpha$- in disease of pancreatic $\beta$-cells. Proc. Natl. Acad. Sci. 95:8898-8903.
  17. Lee. Y., H. Hirose, M. Ohneda, J. H. Johnson, J. D. McGarry and R. H. Unger. 1994. $\beta$-Cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: Impairment in adipocyte- $\beta$-cell relationships. Proc Natl. Acad. Sci. 91:10878-10882.
  18. Chin, S. F., W. Lin, J. M. Storkson, Y. L. Ha and M. W. Pariza. 1992. Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogenens. J. Food Comp. Anal. 5:185-197.
  19. Houseknecht, K. L., J. P. Vanden Heuvel, S. Y. Moya-Camarena, C. P. Portocarrero, L. W. Peck, K. P. Nickel and M. A. Belury. 1998. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem. Biophy. Res. Com. 244:678-682.
  20. Whigham, L. D., M. E. Cook and R. L. Atkinson. 2000. Conjugated linoleic acid: Implications for human health. Pharmacol. Res. 42:503-510.
  21. Rahman, S. M., Y. Wang, H. Yotsumoto, J. Cha, S. Han, S. Inoue and T. Yanagita. 2001. Effects of conjugated linoleic acid on serum leptin concentration, body-fat accumulation, and $\beta$-oxidation of fatty acid in OLETF rats. Nutrition 17:385-390.
  22. Tsuboyama-Kasaoka, N., M. Takahashi, K. Tanemura, H. Kim, T. Tange, H. Okuyama, M. Kasai, S. Ikemoto and O. Ezaki. 2000. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes 49:1534-1542.