Skip to main content
Log in

Rhamnetin-induced suppression of clonal expansion during early stage of adipogenesis

  • Research Articles
  • Drug Actions
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Adipocyte differentiation plays a pivotal role in the progression of obesity which is a major risk factor for several diseases such as diabetes, hypertension and coronary heart disease. In this study, the inhibitory effect of rhamnetin, a flavonoid compound, on adipogenesis in 3T3-L1 cells was investigated. Rhamnetin decreased the accumulation of lipid droplets, and inhibited the elevation of triglyceride content in the adipocytes (IC50 = 17.3 μM). The expressions of PPARγ, C/EBPα, and perilipin, adipocyte differentiation markers, were significantly reduced by rhamnetin. Triglyceride biosynthesis and clonal expansion of adipocytes were completely inhibited during the early stage by rhamnetin. Additionally, rhamnetin significantly decreased the expression of C/EBPβ, an early stage marker. Our results indicate that suppression of clonal expansion during the early stage of adipogenesis by rhamnetin may be associated with inhibition of the C/EBPβ, C/EBPα, and PPARγ pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Arimura, N., Horiba, T., Imagawa, M., Shimizu, M., and Sato, R., The peroxisome proliferator-activated receptor gamma regulates expression of the perilipin gene in adipocytes. J. Biol. Chem., 279, 10070–10076 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Barr, E. L., Cameron, A. J., Balkau, B., Zimmet, P. Z., Welborn, T. A., Tonkin, A. M., and Shaw, J. E., HOMA insulin sensitivity index and the risk of all-cause mortality and cardiovascular disease events in the general population: the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) study. Diabetologia, 53, 79–88 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Bucar, F., Resch, M., Bauer, R., Burits, M., Knauder, E., and Schubert-Zsilavecz, M., 5-Methylflavasperone and rhamnetin from Guiera senegalensis and their antioxidative and 5-lipoxygenase inhibitory activity. Pharmazie, 53, 875–878 (1998).

    PubMed  CAS  Google Scholar 

  • Caro, J. F., Dohm, L. G., Pories, W. J., and Sinha, M. K., Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes. Diabetes Metab. Rev., 5, 665–689 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Choi, S. S., Cha, B. Y., Lee, Y. S., Yonezawa, T., Teruya, T., Nagai, K., and Woo, J. T., Magnolol enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. Life Sci., 84, 908–914 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Cornelius, P., Macdougald, O. A., and Lane, M. D., Regulation of adipocyte development. Annu. Rev. Nutr., 14, 99–129 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Cowherd, R. M., Lyle, R. E., and Mcgehee, R. E., Jr., Molecular regulation of adipocyte differentiation. Semin. Cell Dev. Biol., 10, 3–10 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Gregoire, F. M., Smas, C. M., and Sul, H. S., Understanding adipocyte differentiation. Physiol. Rev., 78, 783–809 (1998).

    PubMed  CAS  Google Scholar 

  • Hastie, C. E., Padmanabhan, S., Slack, R., Pell, A. C., Oldroyd, K. G., Flapan, A. D., Jennings, K. P., Irving, J., Eteiba, H., Dominiczak, A. F., and Pell, J. P., Obesity paradox in a cohort of 4880 consecutive patients undergoing percutaneous coronary intervention. Eur. Heart J., 31, 222–226 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Igarashi, K. and Ohmuma, M., Effects of isorhamnetin, rhamnetin, and quercetin on the concentrations of cholesterol and lipoperoxide in the serum and liver and on the blood and liver antioxidative enzyme activities of rats. Biosci. Biotechnol. Biochem., 59, 595–601 (1995).

    Article  PubMed  CAS  Google Scholar 

  • James, W. P., Astrup, A., Finer, N., Hilsted, J., Kopelman, P., Rossner, S., Saris, W. H., and Van Gaal, L. F., Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet, 356, 2119–2125 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Jiang, H., Zhan, W. Q., Liu, X., and Jiang, S. X., Antioxidant activities of extracts and flavonoid compounds from Oxytropis falcate Bunge. Nat. Prod. Res., 22, 1650–1656 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Kim, Y. K., Kim, Y. S., Choi, S. U., and Ryu, S. Y., Isolation of flavonol rhamnosides from Loranthus tanakae and cytotoxic effect of them on human tumor cell lines. Arch. Pharm. Res., 27, 44–47 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Lee, J., Jung, E., Kim, S., Huh, S., Kim, Y., Byun, S. Y., Kim, Y. S., and Park, D., Isorhamnetin represses adipogenesis in 3T3-L1 cells. Obesity (Silver Spring), 17, 226–232 (2009).

    CAS  Google Scholar 

  • Lee, S. H., Kim, B., Oh, M. J., Yoon, J., Kim, H. Y., Lee, K. J., Lee, J. D., and Choi, K. Y., Persicaria hydropiper (L.) spach and its flavonoid components, isoquercitrin and isorhamnetin, activate the Wnt/β-catenin pathway and inhibit adipocyte differentiation of 3T3-L1 cells. Phytother. Res., 25, 1629–1635 (2011).

    Article  PubMed  CAS  Google Scholar 

  • Martin, R. J., Ramsay, T., and Hausman, G. J., Adipocyte development. Pediatr. Ann., 13, 448–453 (1984).

    PubMed  CAS  Google Scholar 

  • Morrison, R. F. and Farmer, S. R., Insights into the transcriptional control of adipocyte differentiation. J. Cell. Biochem., Suppl 32–33, 59–67 (1999).

  • Ntambi, J. M. and Young-Cheul, K., Adipocyte differentiation and gene expression. J. Nutr., 130, 3122S–3126S (2000).

    PubMed  CAS  Google Scholar 

  • Otto, T. C. and Lane, M. D., Adipose development: from stem cell to adipocyte. Crit. Rev. Biochem. Mol. Biol., 40, 229–242 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Ozipek, M., Calis, I., Ertan, M., and Ruedi, P., Rhamnetin 3-p-coumaroylrhamninoside from Rhamnus petiolaris. Phytochemistry, 37, 249–253 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Rayalam, S., Yang, J. Y., Ambati, S., Della-Fera, M. A., and Baile, C. A., Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res., 22, 1367–1371 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Roberts, A. W., Clark, A. L., and Witte, K. K., Review article: Left ventricular dysfunction and heart failure in metabolic syndrome and diabetes without overt coronary artery disease—do we need to screen our patients? Diab. Vasc. Dis. Res., 6, 153–163 (2009).

    Article  PubMed  Google Scholar 

  • Shin, E., Choi, K. M., Yoo, H. S., Lee, C. K., Hwang, B. Y., and Lee, M. K., Inhibitory effects of coumarins from the stem barks of Fraxinus rhynchophylla on adipocyte differentiation in 3T3-L1 cells. Biol. Pharm. Bull., 33, 1610–614 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Tong, Q. and Hotamisligil, G. S., Molecular mechanisms of adipocyte differentiation. Rev. Endocr. Metab. Disord., 2, 349–355 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Torres, R., Faini, F., Modak, B., Urbina, F., Labbe, C., and Guerrero, J., Antioxidant activity of coumarins and flavonols from the resinous exudate of Haplopappus multifolius. Phytochemistry, 67, 984–987 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Uri, J., Csoban, G., and Viragh, E., The antibacterial effect of the flavonol-dyestuff, rhamnetin. Acta Physiol. Hung., 2, 223–228 (1951).

    PubMed  CAS  Google Scholar 

  • Wagatsuma, A., Upregulation of gene encoding adipogenic transcriptional factors C/EBPalpha and PPARgamma2 in denervated muscle. Exp. Physiol., 91, 747–753 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Wu, J., Lu, H. L., Hu, X. F., Liang, X. Y., Lin, H. H., Wang, H. W., and Fan, X. W., Effect of acylation stimulating protein on the perilipin and adipophilin expression during 3T3-L1 preadipocyte differentiation. Sheng Li Xue Bao, 61, 56–64 (2009).

    PubMed  Google Scholar 

  • Yamamoto, N., Moon, J. H., Tsushida, T., Nagao, A., and Terao, J., Inhibitory effect of quercetin metabolites and their related derivatives on copper ion-induced lipid peroxidation in human low-density lipoprotein. Arch. Biochem. Biophys., 372, 347–354 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Yang, J. Y., Della-Fera, M. A., Rayalam, S., Ambati, S., Hartzell, D. L., Park, H. J., and Baile, C. A., Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci., 82, 1032–1039 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Yun, B. S., Lee, I. K., Kim, J. P., Chung, S. H., Shim, G. S., and Yoo, I. D., Lipid peroxidation inhibitory activity of some constituents isolated from the stem bark of Eucalyptus globulus. Arch. Pharm. Res., 23, 147–150 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y. Y., Li, X., Qian, S. W., Guo, L., Huang, H. Y., He, Q., Liu, Y., Ma, C. G., and Tang, Q. Q., Transcriptional activation of histone H4 by C/EBPbeta during the mitotic clonal expansion of 3T3-L1 adipocyte differentiation. Mol. Biol. Cell, 22, 2165–2174 (2011).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hwan-Soo Yoo.

Additional information

These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ji, SY., Choi, KM., Lee, YS. et al. Rhamnetin-induced suppression of clonal expansion during early stage of adipogenesis. Arch. Pharm. Res. 35, 1083–1089 (2012). https://doi.org/10.1007/s12272-012-0616-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-012-0616-7

Key words

Navigation