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Anti-obesity Effects of Genistein in Female Ovariectomy-induced Obese Mice

난소절제로 비만이 유도된 암컷 쥐에서 제니스테인의 항비만 효과

  • Jeong, Sun-Hyo (Division of Biomedical Engineering & Health, Science Management, College of Science & Technology, Mokwon University)
  • 정선효 (목원대학교 테크노과학대학 의생명.보건학부)
  • Received : 2017.06.15
  • Accepted : 2017.06.29
  • Published : 2017.09.30

Abstract

To investigate whether genistein regulates menopause-induced obesity, it was studied the effects of genistein on anti-obesity effects in female ovariectomized (OVX) mice, an animal model of postmenopausal women. 7-week-old female mice (C57BL/6J) were randomly divided into three groups. All the animals received a high fat diet or a high fat diet supplemented with genistein for 8 weeks and variables and determinants of obesity were measured. The OVX mice had significantly higher body weight and adipose tissue mass than sham mice. However, genistein supplementation reduced body weight, adipose tissue mass, and adipocyte size of OVX mice. The OVX mice treated with genistein had significantly lower levels of serum triglycerides and total cholesterol than the vehicle-treated OVX mice. Lipid accumulation in liver was also markedly decreased by genistein in OVX mice. The results suggest that genistein can effectively prevent adiposity, adipocyte phertrophy, and llipid disorders caused by ovariectomy. Moreover, this study may contribute to the alleviation of metabolic syndrome, including obesity and hyerlipidemia in postmenopausal women.

제니스테인(genistein)이 폐경으로 유도된 비만을 조절하는지를 알아보기 위해 폐경기 여성의 동물모델인 난소절제 암컷 쥐에서 항비만 효과에 대한 제니스테인의 영향을 연구하였다. 7주령의 C57BL/6J 암컷쥐를 무작위로 3그룹으로 나누어 8주 동안 고지방식 사료 또는 제니스테인이 첨가된 고지방식 사료를 섭취시킨 후 비만의 결정요소들을 측정하였다. 난소절제 쥐는 난소가 절제되지 않은 쥐에 비해 몸무게와 지방조직무게가 증가되었다. 그러나 제니스테인의 처리는 난소절제 쥐의 몸무게, 지방조직무게 및 지방세포 크기를 감소시켰다. 난소절제 쥐에 비해 제니스테인이 처리된 난소절제 쥐는 혈청 속의 중성지방과 총 콜레스테롤이 유의적으로 낮아졌다. 또한 난소절제 쥐에서 간조직의 지질성분 축적도 제니스테인에 의해 감소되었다. 이러한 결과는 제니스테인이 난소절제로 유도된 지방과다, 지방세포비대 및 지질이상을 효과적으로 개선시킬 수 있다는 것을 시사하고 있다. 따라서 본 연구는 폐경기 여성의 비만과 고지혈증을 포함한 신진대사 장애의 개선에 공헌할 것이다.

Keywords

References

  1. G. A. Bray, "Risks of obesity", Endocrinol Metab Clin North Am, 32, 787-804 (2003). https://doi.org/10.1016/S0889-8529(03)00067-7
  2. A. Tchernof, J. Calles-Escandon, C. K. Sites, E. T. Poehlman, "Menopause, central body fatness, and insulin resistance: effects of hormone-replacement therapy", Coron Artery Dis, 9, 503-511 (1998). https://doi.org/10.1097/00019501-199809080-00006
  3. R. R. Wing, K. A. Matthews, "Weight gain at the time of menopause", Arch Intern Med, 151, 97-102 (1991). https://doi.org/10.1001/archinte.1991.00400010111016
  4. N. Geary, L. Asarian, "Estradiol increases glucagon's satiating potency in ovariectomized rats", Am J Physiol Regul Integr Comp Physiol, 281, R1290-R1294 (2001). https://doi.org/10.1152/ajpregu.2001.281.4.R1290
  5. S. Jeong, M. Yoon, "Inhibition of the actions of peroxisome proliferatoractivated receptor ${\alpha}$ on obesity by estrogen", Obesity (Silver Spring), 15, 1430-1440 (2007). https://doi.org/10.1038/oby.2007.171
  6. M. S. Kurzer, X. Xu, "Dietary phytoestrogens", Annu Rev Nutr, 17, 353-381 (1997). https://doi.org/10.1146/annurev.nutr.17.1.353
  7. J. W. Anderson, B. M. Smith, C. S. Washnock, "Cardiovascular and renal benefits of dry bean and soybean intake", Am J Clin Nutr, 70(3 Suppl), 464S-474S (1999). https://doi.org/10.1093/ajcn/70.3.464s
  8. P. M. Martin, K. B. Horwitz, D. S. Ryan, W. L. McGuire, "Phytoestrogen interaction with estrogen receptors in human breast cancer cells", Endocrinology, 103(5), 1860-1867 (1978 Nov). https://doi.org/10.1210/endo-103-5-1860
  9. Z. Zhang, C. Z. Wang, G. J. Du, L. W. Qi, T. Calway, T. C. He, W. Du, C. S. Yuan, "Genistein induces G2/M cell cycle arrest and apoptosis via atm/p53-dependent pathway in human colon cancer cell", Int J Oncol, 1, 289- 296 (2013).
  10. K. A. Hwang, N. H. Kang, B. R. Yi, H. R. Lee, M. A. Park, K. C. Choi, "Genistein, a soy phytoestrogen, prevents the growth of BG-1 ovarian cancer cells induced by 17beta-estradiol or bisphenol A via the inhibition of cell cycle progression", Int J Oncol, 2, 733-740 (2013).
  11. F. Afaq, H. Mukhtar, "Botanical antioxidants in the prevention of photocarcinogenesis and photoaging", Exp Dermatol, 15(9), 678-684 (2006). https://doi.org/10.1111/j.1600-0625.2006.00466.x
  12. Z. Fu, E. R. Gilbert, L. Pfeiffer, Y. Zhang, Y. Fu, D. Liu, "Genisteinameliorateshyperglycemia in a mouse model of nongenetic type 2 diabetes", Appl Physiol Nutr Metab, 37(3), 480-488 (2012). https://doi.org/10.1139/h2012-005
  13. Z. Fu, D. Liu, "Long-termexposure to genistein improves insulin secretory function of pancreatic beta-cells", Eur J Pharmacol, 616(1-3), 321-327 (2009). https://doi.org/10.1016/j.ejphar.2009.06.005
  14. H. Marini, L. Minutoli, F. Polito, A. Bitto, D. Altavilla, M. Atteritano, A. Gaudio, S. Mazzaferro, A. Frisina, N. Frisina, C. Lubrano, M. Bonaiuto, R. D'Anna, M. L. Cannata, F. Corrado, E. B. Adamo, S. Wilson, F. Squadrito, "Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial", Ann Intern Med, 146(12), 839-847 (2007). https://doi.org/10.7326/0003-4819-146-12-200706190-00005
  15. A. Bitto, B. P. Burnett, F. Polito, H. Marini, R. M. Levy, M. A. Armbruster, L. Minutoli, V. Di Stefano, N. Irrera, S. Antoci, R. Granese, F. Squadrito, D. Altavilla, "Effects of genistein aglycone in osteoporotic, ovariectomizedrats: a comparison with alendronate, raloxifene and oestradiol", Br J Pharmacol, 155(6), 896-905 (2008). https://doi.org/10.1038/bjp.2008.305
  16. A. Bitto, V. Arcoraci, A. Alibrandi, R. D'Anna, F. Corrado, M. Atteritano, L. Minutoli, D. Altavilla, F. Squadrito, "Visfatin correlates with hot flashes in postmenopausal women with metabolic syndrome: effects of genistein", Endocrine, 55(3), 899-906 (2017). https://doi.org/10.1007/s12020-016-0968-8
  17. S. Reinwald, L. P. Mayer, P. B. Hoyer, C. H. Turner, S. Barnes, C. M. Weaver, "A longitudinal study of the effect of genistein on bone in two different murine models of diminished estrogen-producing capacity", J Osteoporos, 2010(pii: 145170), 14 pages (2010). https://doi.org/10.4061/2010/145170
  18. Y. Zhang, Q. Li, H. Y. Wan, W. G. Helferich, M. S. Wong, "Genistein and a soy extract differentially affect three-dimensional bone parameters and bone-specific gene expression in ovariectomized mice", J Nutr, 139(12), 2230-2236 (2009). https://doi.org/10.3945/jn.109.108399
  19. M. Yoon, S. Jeong, "$17{\beta}$-estradiol prevents the expression of $CEBP{\alpha}$-mediated adipocyte marker genes in female ovariectomized C57BL/6 mice", J Exp Biomed Sci, 14, 131-137 (2008).
  20. S. Jeong, H. Choi, M. Yoon, "Morpological changes in adipose and liver tissue by $17{\beta}$-estradiol in female ovariectomized C57BL/6J mice", J Exp Biomed Sci, 13, (2007).
  21. T. Fukunaga, Y. Ishida, M. Konodo, "Subcutannious fat and muscle distrbution patterns in middle and aged Japanese", J Them Bid, 18, 303-306 (1993).
  22. E. T. Poehlman, M. J. Toth, A. W. Gardner, "Changes in energy balance and body composition at menopause: a controlled longitudinal study", Ann Intern Med, 123, 673-675 (1995). https://doi.org/10.7326/0003-4819-123-9-199511010-00005
  23. L. Liu, Y. Li, T. O. Tollefsbol, "Gene-environment interactions and epigenetic basis of human diseases", Curr Issues Mol Biol, 10, 25-36 (2008).
  24. E. D. Rosen, B. M. Spiegelman, "Molecular regulation of aipogenesis", Annu Rev Cell Dev Biol, 16, 145-171 (2000). https://doi.org/10.1146/annurev.cellbio.16.1.145
  25. K. N. Frayn, "Insulin resistance lipid metabolism", Cur Opinion Lipidol, 4, 197-204 (1993). https://doi.org/10.1097/00041433-199306000-00004
  26. K. Yagi, D. Kondo, Y. Okazaki, K. Kano, "A novel preadipocyte cell line established from mouse adult mature adipocytes", Biochemica and Biophysical Research Communications, 321(4), 967-974 (2004). https://doi.org/10.1016/j.bbrc.2004.07.055
  27. Y. Takahashi, T. O. Odbayar, T. Ide, "A comparative analysis of genistein and daidzein in affecting lipid metabolism in rat liver", J Clin Biochem Nutr, 44(3), 223-30 (2009). https://doi.org/10.3164/jcbn.08-211
  28. L. Pilote, K. Dasgupta, V. Guru, K. H. Humphries, J. McGrath, C. Norris, D. Rabi, J. Tremblay, A. Alamian, T. Barnett, J. Cox, W. A. Ghali, S. Grace, P. Hamet, T. Ho, S. Kirkland, M. Lambert, D. Libersan, J. O'Loughlin, G. Paradis, M. Petrovich, V. Tagalakis, "A comprehensive view of sex-specific issues related to cardiovascular disease", Canadian Medical Association Journal, 176, S1-S44 (2007).
  29. Y. Y. Tan, G. C. Gast, Y. T. van der Schouw, "Gender differences in risk factors for coronary heart disease", Maturitas, 65, 149-160 (2010). https://doi.org/10.1016/j.maturitas.2009.09.023
  30. M. Yoon, S. Jeong, H. Lee, M. Han, J. Kang, E. Y. Kim, M. Kim, G. T. Oh, "Fenofibrate improves lipid metabolism and obesity in ovariectomized LDL receptornull mice", Biochem Biophys Res Commun, 302, 29-34 (2003). https://doi.org/10.1016/S0006-291X(03)00088-3
  31. S. Jeong, M. Kim, M. Han, H. Lee, J. Ahn, M. Kim, Y-H. Song, C. Shin, K-H. Nam, T. Kim, G. T. Oh, M. Yoon, "Fenofibrate prevents obesity and hypertriglyceridemia in low-density lipoproteinnull mice", Metabolism, 53, 607-613 (2004). https://doi.org/10.1016/j.metabol.2003.12.010
  32. S. Jeong, M. Yoon, "Troglitazone lowers serum triglycerides with sexual dimorphism in C57BL/6J mice", J Exp Biomed Sci, 12, 65-72 (2006).
  33. D. Goodman-Gruen, D. Kritz-Silverstein, "Usual dietary isoflavone intake and body composition in postmenopausal women", Menopause, 10(5), 427-432 (2003). https://doi.org/10.1097/01.GME.0000058866.35869.B4
  34. M. Heim, O. Frank, G. Kampmann, N. Sochocky, T. Pennimpede, P. Fuchs, W. Hunziker, P. Weber, I. Martin, I. Bendik, "The phytoestrogen genistein enhances osteogenesis and represses adipogenic differentiation of human primary bone marrow stromal cells", Endocrinology, 145(2), 848-859 (2004). https://doi.org/10.1210/en.2003-1014
  35. M. L. Ricketts, D. D. Moore, W. J. Banz, O. Mezei, N. F. Shay, "Molecular mechanisms of action of the soy isoflavones includes activation of promiscuous nuclear receptors", A review, J Nutr Biochem, 16(6), 321-30 (2005). https://doi.org/10.1016/j.jnutbio.2004.11.008
  36. S. E. Campbell, K. A. Mehan, R. J. Tunstall, M. A. Febbraio, D. Cameron-Smith, "17beta-estradiol upregulates the expression of peroxisome proliferatoractivated receptor alpha and lipid oxidative genes in skeletal muscle", J Mol Endocrinol, 31(1), 37-45 (2003). https://doi.org/10.1677/jme.0.0310037
  37. K. Toda, K. Takeda, S. Akira, T. Saibara, T. Okeda, S. Onishi, Y. Shizuta, "Alterations in hepatic expression of fatty-acid metabolizing enzymes in ArKO mice and their reversal by the treatment with 17 beta-estradiol or a peroxisome proliferator", J Steroid Biochem Mol Biol, 79, 11-17 (2001). https://doi.org/10.1016/S0960-0760(01)00135-2