Open Access

Farnesyltransferase inhibitors prevent HIV protease inhibitor (lopinavir/ritonavir)-induced lipodystrophy and metabolic syndrome in mice

  • Authors:
    • Tomokazu Tanaka
    • Harumasa Nakazawa
    • Naohide Kuriyama
    • Masao Kaneki
  • View Affiliations

  • Published online on: November 17, 2017     https://doi.org/10.3892/etm.2017.5526
  • Pages:1314-1320
  • Copyright: © Tanaka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Highly active antiretroviral therapy (HAART) has successfully reduced the mortality rate of patients with human immune deficiency virus (HIV) and HIV protease inhibitors (HIV PIs) are key components of HAART. Complications of HAART, particularly those associated with HIV PIs including lipodystrophy and metabolic disturbance, have emerged as an important public health issue. No specific treatment is available to prevent and/or treat HIV PI‑associated lipodystrophy and metabolic syndrome. The present study demonstrated that a relatively low‑dose of farnesyltransferase inhibitor (FTI), tipifarnib (3 mg/kg/day, subcutaneous injection) and lonafarnib (5 mg/kg/day, subcutaneous injection), prevented the onset of lipodystrophy and metabolic syndrome induced by the combination of two HIV PIs, lopinavir (50 mg/kg/day, intraperitoneal injection) and ritonavir (12.5 mg/kg/day, intraperitoneal injection), in mice. Consistent with previous studies, treatment with lopinavir/ritonavir for 2 weeks decreased body weight, adipose tissue mass, levels of plasma adiponectin and leptin, and increased plasma levels of triglycerides, total cholesterol and insulin. Tipifarnib and lonafarnb prevented or ameliorated all of these alterations in the HIV PI‑treated mice. These data identify FTIs as a novel potential strategy to prevent or treat HIV PI‑associated lipodystrophy and metabolic syndrome in HIV‑infected patients on HAART.

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February 2018
Volume 15 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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APA
Tanaka, T., Nakazawa, H., Kuriyama, N., & Kaneki, M. (2018). Farnesyltransferase inhibitors prevent HIV protease inhibitor (lopinavir/ritonavir)-induced lipodystrophy and metabolic syndrome in mice. Experimental and Therapeutic Medicine, 15, 1314-1320. https://doi.org/10.3892/etm.2017.5526
MLA
Tanaka, T., Nakazawa, H., Kuriyama, N., Kaneki, M."Farnesyltransferase inhibitors prevent HIV protease inhibitor (lopinavir/ritonavir)-induced lipodystrophy and metabolic syndrome in mice". Experimental and Therapeutic Medicine 15.2 (2018): 1314-1320.
Chicago
Tanaka, T., Nakazawa, H., Kuriyama, N., Kaneki, M."Farnesyltransferase inhibitors prevent HIV protease inhibitor (lopinavir/ritonavir)-induced lipodystrophy and metabolic syndrome in mice". Experimental and Therapeutic Medicine 15, no. 2 (2018): 1314-1320. https://doi.org/10.3892/etm.2017.5526