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Adipose tissue homeostasis is deeply disrupted by doxorubicin treatment

Introduction

Doxorubicin is an anthracyclin antibiotic commonly used in chemotherapy against several types of cancer, however it has a great number of side effects [1, 2]. Doxorubicin treatment reduces body weight, affects total cholesterol, free fatty acids and the level of fasting blood glucose [3]. Furthermore this chemotherapy can act to damage the adipocytes increasing the development of insulin resistance in peripheral tissues [1]. Our aim was to investigate the doxorubicin effects on adipocyte tissue and its functions.

Materials and methods

We performed in vivo studies with 20 male rats, 10 treated 72 hours before the sacrifice with 15 mg/kg doxorubicin and 10 treated with PBS. We took the retroperitoneal adipocyte tissue to measure lipogenesis, lipolysis, and glucose uptake. We also had an in vitro testing using 3T3-L1 cells treated with doxorubicin to perform toxicity and lipolysis assays.

Results

Our results showed that in rats, lipogenesis was significantly decreased and lipolysis was also decreased. The glucose uptake test was significantly decreased and the free fatty acids were increased. In vitro assay showed that higher doses (10 and 100 nM concentrations) were toxic, inducing over 90% cellular apoptosis. Lipolysis in vitro was decreased when the cells were treated with 10 nM for 30 minutes; in this interval this concentration was not toxic because the LDH activity was not modified.

Conclusions

We can conclude that doxorubicin has many effects upon adipocyte tissue homeostasis, decreasing lipolysis and lipogenesis, glucose uptake and inducing cellular apoptosis in high concentrations, being able to change its function. We are still investigating the molecular mechanisms of this process.

References

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    Arunachalam S, Tirupathi Pichiah PB, Achiraman S: Doxorubicin treatment inhibits PPARgamma and may induce lipotoxicity by mimicking a type 2 diabetes-like condition in rodent models. FEBS Lett. 2013, 587: 105-110. 10.1016/j.febslet.2012.11.019.

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    Buttiglieri S, Ruella M, Risso A, Spatola T, Silengo L, Avvedimento EV, Tarella C: The aging effect of chemotherapy on cultured human mesenchymal stem cells. Exp Hematol. 2011, 39: 1171-1181. 10.1016/j.exphem.2011.08.009.

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    Asensio-Lopez MC, Lax A, Pascual-Figal DA, Valdes M, Sanchez-Mas J: Metformin protects against doxorubicin-induced cardiotoxicity: Involvement of the adiponectin cardiac system. Free Radic Biol Med. 2011, 51: 1861-1871. 10.1016/j.freeradbiomed.2011.08.015.

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Acknowledgements

Foundation of Research Support of the State of São Paulo (FAPESP) National Center of Research and technological development (CNPQ)

Author information

Correspondence to Helena Batatinha.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Keywords

  • Cholesterol
  • Insulin Resistance
  • Adipose Tissue
  • Doxorubicin
  • Free Fatty Acid