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Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia

  • Authors:
    • Ruihua Zhong
    • Wenjie Yang
    • Guoting Li
    • Shuwu Xie
    • Xiangjie Guo
    • Jieyun Zhou
    • Bingtao Ren
    • Yan Zhu
  • View Affiliations / Copyright

    Affiliations: Lab of Reproductive Pharmacology, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, P.R. China
    Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 24
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    Published online on: November 23, 2022
       https://doi.org/10.3892/etm.2022.11723
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Abstract

Cachexia, a complex disorder that results in depletion of adipose tissue and skeletal muscle, is driven by anorexia, metabolic abnormalities and inflammation. There are limited therapeutic options for this syndrome. Previous evidence has demonstrated that increasing adipose tissue may improve quality of life and survival outcomes in cachexia. Cisplatin, as a chemotherapy drug, also causes cachexia during antitumor therapy due to its adverse effects. To establish a rat model of cachexia, the animals were intraperitoneally treated with cisplatin at doses of 1, 2 and 3 mg/kg, and the rats that responded to cisplatin at the optimal dose were used to test the effect of nomegestrol acetate (NOMAc). Rats that were assessed to be sensitive to cisplatin were randomly grouped and intragastrically administered vehicle, 5 or 10 mg/kg megestrol acetate (MA) or 2.5, 5 or 10 mg/kg NOMAc. The body weights and food consumption of the rats were assessed. Serum IL‑6 and TNF‑α levels were assessed using ELISA. The protein expression levels of adipose triglyceride lipase (ATGL), hormone‑sensitive lipase (HSL), peroxisome proliferator activated receptor γ (PPARγ), fatty acid synthase (FASN) and sterol regulatory element‑binding protein‑1 (SREBP‑1) from inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) were evaluated using western blotting. The optimal way to establish a chemotherapy‑induced rat model of cachexia demonstrated in the present study was to intraperitoneally administer the rats with 2 mg/kg cisplatin for 3 consecutive days. NOMAc (2.5, 5 mg/kg) and MA (10 mg/kg) were able to significantly ameliorate the loss of body weight in the cisplatin‑induced cachectic rats. NOMAc significantly reduced the serum levels of TNF‑α at 10 mg/kg. Morphologically, iWAT atrophy, with a remarkable reduction in adipocyte volume, was observed in the cisplatin‑induced cachectic rats, but the effects were reversed by administering 5, 10 mg/kg NOMAc or 10 mg/kg MA. Furthermore, 2.5 mg/kg NOMAc markedly reduced the protein expression levels of the lipolysis genes HSL and ATGL, and 5 mg/kg NOMAc markedly enhanced the protein expression levels of adipogenesis genes, including FASN, SREBP‑1 and PPARγ in iWAT but not in eWAT. NOMAc was demonstrated to improve cachexia at lower doses compared with MA. Overall, NOMAc is likely to be a promising candidate drug for ameliorating cancer cachexia induced by cisplatin.
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Copy and paste a formatted citation
Spandidos Publications style
Zhong R, Yang W, Li G, Xie S, Guo X, Zhou J, Ren B and Zhu Y: Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia. Exp Ther Med 25: 24, 2023.
APA
Zhong, R., Yang, W., Li, G., Xie, S., Guo, X., Zhou, J. ... Zhu, Y. (2023). Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia. Experimental and Therapeutic Medicine, 25, 24. https://doi.org/10.3892/etm.2022.11723
MLA
Zhong, R., Yang, W., Li, G., Xie, S., Guo, X., Zhou, J., Ren, B., Zhu, Y."Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia". Experimental and Therapeutic Medicine 25.1 (2023): 24.
Chicago
Zhong, R., Yang, W., Li, G., Xie, S., Guo, X., Zhou, J., Ren, B., Zhu, Y."Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia". Experimental and Therapeutic Medicine 25, no. 1 (2023): 24. https://doi.org/10.3892/etm.2022.11723
Copy and paste a formatted citation
x
Spandidos Publications style
Zhong R, Yang W, Li G, Xie S, Guo X, Zhou J, Ren B and Zhu Y: Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia. Exp Ther Med 25: 24, 2023.
APA
Zhong, R., Yang, W., Li, G., Xie, S., Guo, X., Zhou, J. ... Zhu, Y. (2023). Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia. Experimental and Therapeutic Medicine, 25, 24. https://doi.org/10.3892/etm.2022.11723
MLA
Zhong, R., Yang, W., Li, G., Xie, S., Guo, X., Zhou, J., Ren, B., Zhu, Y."Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia". Experimental and Therapeutic Medicine 25.1 (2023): 24.
Chicago
Zhong, R., Yang, W., Li, G., Xie, S., Guo, X., Zhou, J., Ren, B., Zhu, Y."Nomegestrol acetate ameliorated adipose atrophy in a rat model of cisplatin‑induced cachexia". Experimental and Therapeutic Medicine 25, no. 1 (2023): 24. https://doi.org/10.3892/etm.2022.11723
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