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Mitochondrial DNA decrease in subcutaneous adipose tissue of HIV-infected individuals with peripheral lipoatrophy.

C M Shikuma1, N Hu, C Milne

  • 1Pacific Biomedical Research Center, John A. Burns School of Medicine, University of Hawaii-Manoa, Honolulu, Hawaii 96816, USA. shikuma@hawaii.edu

AIDS (London, England)
|October 2, 2001
PubMed
Summary
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Peripheral fat wasting in HIV patients on nucleoside reverse transcriptase inhibitor (NRTI)-containing highly active antiretroviral therapy (HAART) is linked to reduced mitochondrial DNA (mtDNA) content in subcutaneous fat. No large mtDNA deletions or insertions were observed.

Area of Science:

  • Biochemistry
  • Virology
  • Genetics

Background:

  • Highly active antiretroviral therapy (HAART) including nucleoside reverse transcriptase inhibitors (NRTIs) can cause peripheral fat wasting (lipodystrophy) in HIV-infected patients.
  • The underlying mechanisms of NRTI-induced lipodystrophy are not fully understood.
  • Mitochondrial dysfunction has been implicated in the pathogenesis of lipodystrophy.

Purpose of the Study:

  • To investigate the association between peripheral fat wasting in HIV patients on NRTI-containing HAART and subcutaneous adipose tissue mitochondrial DNA (mtDNA) content.
  • To determine if large mtDNA deletions or insertions are present in patients with lipodystrophy.

Main Methods:

  • A cross-sectional study comparing four cohorts: HIV patients with lipodystrophy on NRTI-HAART, HIV patients without lipodystrophy on NRTI-HAART, HIV patients treatment-naive, and HIV-negative individuals.

Related Experiment Videos

  • Quantitative polymerase chain reaction (PCR) was used to measure mtDNA content in subcutaneous fat from the neck, abdomen, and thigh.
  • Analysis focused on the amplification of three distinct mtDNA fragments.

    • Main Results:

    • Subcutaneous adipose tissue mtDNA content was significantly decreased in HIV-infected patients with peripheral fat wasting receiving NRTI-containing HAART compared to all control groups.
    • No evidence of large deletions or insertions in the mtDNA was detected in any of the study participants.
    • These findings suggest a specific impact on mtDNA quantity rather than structural integrity.

    Conclusions:

    • Peripheral fat wasting associated with NRTI-containing HAART in HIV-infected individuals is characterized by a reduction in subcutaneous adipose tissue mtDNA content.
    • The observed decrease in mtDNA content may contribute to the pathophysiology of lipodystrophy.
    • Further research is warranted to explore the precise role of mitochondrial dysfunction in HAART-associated lipodystrophy.