Hibiscus Sabdariffa L. Inhibits the Insulin Signaling in Adipogenesis

지방세포분화에서 Hibiscus 추출물에 의한 Insulin signaling 억제효과

  • Kim, Jin-Kyung (Vestibulocochlear Research Center & Department of Microbiology, Wonkwang University) ;
  • Song, Jeong-Hoon (Plastic & Reconstructive Surgery, Wonkwang University School of Medicine)
  • 김진경 (원광대학교 의과대학 전정와우센터) ;
  • 송정훈 (원광대학교 성형외과학교실)
  • Published : 2007.02.25

Abstract

Hibiscus sabdariffa L., a tropical beverage material, is used commonly as in folk medicine against hypertension, pyrexia, inflammation, liver disorders, and obesity. However, the mechanism by which Hibiscus sabdariffa L. modulates adipogenic differentiation is remained to be elusive. This report was designed to investigate the inhibitory effect of Hibiscus extract on insulin signaling pathway during adipocyte differentiation in 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were differentiated with isobutylmethylxanthine, dexamethasone, and insulin (MDI) and followed by the addition of Hibiscus extract. Treatment with Hibiscus resulted in a decrease of lipid droplet accumulation, which was suppressed by PI-3 kinase inhibitor wortmannin in 3T3-L1 preadipocytes. Also, Hibiscus extract markedly attenuated the mRNA expression of adipogenic transcriptional factor PPAR${\gamma}$ and adipogenic hormon Leptin during adipogenesis. However, it did not affect the expression of adiponectin in 3T3-L1 preadipocytes differentiated with MDI mixture. Furthermore, Adipogenic differentiation by MDI mixture increased the phosphorylation and expression of PI3-Kinase and Akt in 3T3 preadipocytes, which was markedly suppressed by Hibiscus extract treatment. Taken together, our results suggest that Hibiscus extract suppressed the adipogenic differentiation of 3T3 preadipocytes through activation of PI3-Kinase and Akt signaling pathway.

Keywords

References

  1. Kuczmarski, R.J., Flegal, K.M., Campbell, S.M., Johnson, C.L. Increasing prevalence of overweight among US adults. The National Health and Nutrition Examination Sureveys. 1960 to 1991. JAMA. 272:205-211, 1994 https://doi.org/10.1001/jama.272.3.205
  2. Wolf, A.M., Colditz, G.A. Social and economic effects of body weight in the United States. Am. J. Clin. Nutr. 63: 466S-469S, 1996 https://doi.org/10.1093/ajcn/63.3.466
  3. Pi-Sunyer, F.X. Medical hazards of obesity. Ann Intern Med. 19(7 Pt 2):655-660, 1993
  4. Update: Prevalence of overweight among children, adolescents, and adults-United States. Morb Mortal Wkly Rep. 46: 199-202, 1997
  5. Sheard, N.F. Moderate changes in weight and physical activity can prevent or delay the development of type 2 diabetes mellitus in susceptible individuals. Nutr. Rev. 61: 76-79, 2003 https://doi.org/10.1301/nr.2003.febr.76-79
  6. Anne, W. Harmon, Joyce, B. Harp. Differentiatial effects of flavonoids on 3T3-L1 adipogenesis and lipolysis. Am J Physiol Cell Physiol. 280:C807-C813, 2001 https://doi.org/10.1152/ajpcell.2001.280.4.C807
  7. Swen, W., Ying, W., Frank, T. Anti-obesity effects of green tea: from beside to bench. Mol. Nutr. Food Res. 50: 176-187, 2006 https://doi.org/10.1002/mnfr.200500102
  8. Haji, Raraji, Haji, Takhani. The effect of sour tea (Hibiscus sabdariffa L) on essential hypertension. 65:231-236, 1999
  9. Onyenekwe, P.C., Ajani, E.O., Ameh, D.A., Gamaniel, K.S. Antihypertensive effect of roselle (Hibiscus sabdariffa) calyx infusion in spontaneously hypertensive rats and a comparison of its toxicity with that in Wistar rats. Cell Biochem Funct. 17(3):199-206, 1999 https://doi.org/10.1002/(SICI)1099-0844(199909)17:3<199::AID-CBF829>3.0.CO;2-2
  10. El-saadany, S.S., Sitohy, M. Z., Labib, S.M. Biochemical dynamics and hypo cholesterolemic action of Hibiscus sabdariffa (Karkade). Nahrung. 35:567-576, 1991 https://doi.org/10.1002/food.19910350603
  11. Hansawasdi, C., Kawabata, J., Kasai, T. Alpha-amylase inhibitors from roselle (Hibiscus sabdariffa Linn.) tea. Biosci Biotechnol Biochem. 64(5):1041-1043, 2000 https://doi.org/10.1271/bbb.64.1041
  12. Farombi, E.O., Fakoya, A. Free radical scavenging and antigenotoxic activities of natural phenolic compounds in dried flowers. Mol Nutr Food Res. 49(12):1120-1128, 2005 https://doi.org/10.1002/mnfr.200500084
  13. Hirunpanich, V., Utaipat, A., Morales, N.P,, Bunyapraphatsara, N., Sato, H., Herunsale, A., Suthisisang, C. Hypocholesterolemic and antioxidant effects of aqueous extracts from the dried calyx of Hibiscus sabdariffa L in hypercholesterolemic rats. J Ethnopharmacol. 103(2):252-260, 2006 https://doi.org/10.1016/j.jep.2005.08.033
  14. Cornelius, P., MacDounald, O.A,, Lane, M.D. Regulation of adipocyte development. Annu Rev Nutr. 14:99-129, 1994 https://doi.org/10.1146/annurev.nu.14.070194.000531
  15. Regina, P.B., Kim, J.B., Erding, H., Soner, A., Bruce, M.S. Adipocyte differentiation: a transcriptional regulatory cascade. 8:826-832, 1996 https://doi.org/10.1016/S0955-0674(96)80084-6
  16. Lin, F.T., Lane, M.D. CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3- L1 adipocyte differentiation program. Proc Natl Acad Sci U S A. 91(19):8757-8761, 1994
  17. Rosen, E.D., Hsu, C.H., Wang, X., Sakai, S., Freeman, M. W., Gonzalez, F.J., Spiegelman. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev. 16(1):22-26, 2002 https://doi.org/10.1101/gad.948702
  18. Smith, P.J., Wise, L.S., Berkowit, R.C., Rubin, C.S. Insuli-like growth factor-I is an essential regulatior of the differentiation of 3T3-L1 adipocytes. J Biol Chem. 263:9402-9408, 1988
  19. Cheatham, B., Kahn, C.R. Insulin action and the insulin signaling network. Endocr Rev. 16:117-142, 1995
  20. Czech, M.P. Fat targets for insulin signaling. Mol Cell. 9: 695-696, 2002 https://doi.org/10.1016/S1097-2765(02)00509-9
  21. Birkenmeier, E.H., Gwynn, B., Howard, S., Jerry, J., Gordon, J.I. Landschulz, W.H., McKnight, S.L. Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev. 3(8):1146-1156, 1989 https://doi.org/10.1101/gad.3.8.1146
  22. Johnson, P.F., Landschulz, W.H., Graves, B.J., McKnight, S.L. Identification of a rat liver nuclear protein that binds to the enhancer core element of three anival viruses. Gene Dev. 1:133-146, 1987 https://doi.org/10.1101/gad.1.2.133
  23. McKnight, S.L. Transcriptional regulation. cold spring Harbor Lab. Press, Plainview. 771-795. 1992
  24. Fiedman, J.M., Halaas, J.L. Leptin and the regulation of body weight in mammals. nature. 395:763-770, 1998 https://doi.org/10.1038/27376
  25. He, Y, Chen, H., Quon, M.J., Reitman, M. The mouse obese gene. Genomic organization, promoter activity, and activation by CCAAT /enhancer-binding protein alpha. J Biol Chem. 270:28887-28891, 1995 https://doi.org/10.1074/jbc.270.48.28887
  26. Bluher, M., Michael, M.D., Peroni, O.D., Ueki, K., Carter, N., Kahn, B.B., Kahn, C.R. Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev. Cell 3:25-38, 2002 https://doi.org/10.1016/S1534-5807(02)00199-5
  27. Bluher, M., Patti, M.E., Gesta, S., Kahn, B.B., Kahn, C.R. Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knockout mice is associated with differences in patterns of gene expression, J. Biol. Chem. 2004