Mitochondrial damage in adipose tissue of untreated HIV-infected patients

Garrabou, Glòriaa,*; López, Sòniaa,*; Morén, Constanzaa; Martínez, Estebanb; Fontdevila, Joanc; Cardellach, Francesca; Gatell, Josep Mariab; Miró, Òscara

AIDS:
doi: 10.1097/QAD.0b013e3283423219
Basic Science: Concise Communications
Abstract

Objective: Antiretrovirals, especially thymidine-analogue nucleoside reverse transcriptase inhibitors (tNRTIs), may cause the mitochondrial damage in adipose tissue that has been associated with lipodystrophy development. HIV itself may damage blood cell mitochondria. However, the viral capacity to induce adipose tissue mitochondrial lesion is still a matter of doubt. We aimed to assess whether untreated HIV infection was associated with adipose tissue mitochondrial abnormalities.

Design: Single-site, cross-sectional, controlled observational and exploratory study without intervention.

Methods: We included 24 uninfected controls and 18 HIV-infected patients with undetectable viral load and no clinical signs of lipodystrophy stratified as antiretroviral naive (n = 11) or at least 6-month antiviral-treated with a double NRTI combination, including lamivudine plus one tNRTI (n = 7). Subcutaneous adipose tissue was homogenated to determine mtDNA content by rtPCR and mitochondrial function per mitochondria through the spectrophotometric measurement of cytochrome c oxidase activity normalized by citrate synthase amount (COX/citrate synthase). Differences in mitochondrial parameters among groups were sought to determine the contribution of HIV and antiretrovirals to mitochondrial alterations.

Results: Compared with uninfected controls (arbitrarily assigned 100%), naive individuals presented a marked decrease in adipose tissue mtDNA content and COX/citrate synthase function (62 and 75% remaining content/activity, P < 0.001 and P < 0.05). Antiretrovirals did not increase this impairment (69 and 70% remaining content/activity, P < 0.05 compared to controls and P = not significant compared to naives). Additionally, molecular and functional mitochondrial parameters were positively correlated (P < 0.05).

Conclusion: In nonlipodystrophic HIV-infected naive patients, viral infection is associated with adipose tissue mtDNA decrease and mitochondrial dysfunction independently of antiretroviral treatment.

Author Information

aMitochondrial Research Laboratory, Internal Medicine Department, Muscle Research Unit, IDIBAPS, University of Barcelona, Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Valencia), Spain

bInfectious Diseases Department, Spain

cPlastic Surgery Department, Hospital Clinic of Barcelona, Barcelona, Catalonia, Spain.

*Gloria Garrabou and Sonia Lopez contributed equally to the writing of the article.

Received 8 July, 2010

Revised 13 September, 2010

Accepted 1 November, 2010

Correspondence to Dr Glòria Garrabou, Mitochondrial Research Laboratory 413 IDIBAPS, Hospital Clinic of Barcelona, Villarroel 170, 08036 Barcelona, Catalonia, Spain. Tel: +34 932275400x2907; fax: +34 932275693; e-mail: garrabou@clinic.ub.es

© 2011 Lippincott Williams & Wilkins, Inc.