6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 25–28 October 2004 - Washington, DC, USA

MITOCHONDRIAL STUDIES IN ADIPOSE TISSUE OF HIV-INFECTED PATIENTS WITHOUT FAT REDISTRIBUTION

Antiviral Therapy 2004; 9(6):L20 (abstract no. 27)

S López¹, G Garrabou¹, E Martínez², P Domingo³, J Fontdevila⁴, JM Gatell², AB Infante¹, X Gallart⁵, A Milinkovic², F Cardellach¹, J Casademont¹ and Ò Miró^1
1Mitochondrial Research Laboratory, Muscle Research Unit, Department of Internal Medicine, Hospital Clinic, IDIBAPS, Barcelona, Catalonia, Spain; ²Department of Infectious Diseases, Hospital Clinic, IDIBAPS, Barcelona, Catalonia, Spain; ³Infectious Diseases Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Catalonia, Spain; ⁴Department of Plastic Surgery, Hospital Clinic, IDIBAPS, Barcelona, Catalonia, Spain; and ⁵Department of Orthopaedic Surgery and Traumatology (ICMEQ), Hospital Clinic, IDIBAPS, Barcelona, Catalonia, Spain

OBJECTIVES: Mitochondrial (mt) DNA depletion in adipose tissue (AT) has been reported in patients with highly active antiretroviral therapy (HAART)-related lipodystrophy (LD). However, few studies have focused on the role of HIV itself or HAART in the AT mtDNA decrease. Similarly, the effects of mtDNA depletion on mitochondrial respiratory chain (MRC) function has not been evaluated. The aim of the study was to assess the mitochondrial amount, function and mtDNA content in AT from HIV patients prior to the development of LD.

METHODS: We studied AT mitochondria of 20 healthy controls (group A) and 17 HIV patients, the latter stratified in two subgroups: one antiretroviral naïve (n=8, group B) and the other one on HAART (n=9, group C). AT obtained from abdomen, thigh or arm was immediately frozen in liquid nitrogen and stored at –80°C until analysis. We determined the mitochondrial amount in the AT homogenate by the spectrophotometric assay of citrate synthase (CS) activity, as well as the mitochondrial respiratory chain (MRC) function, by the specific activity of cytochrome c oxidase (COX, complex IV of the MRC). MtDNA was measured by quantitative real-time PCR and expressed as the mtDNA to nuclear DNA ratio.

RESULTS: The mitochondrial amount was unaltered among groups. Conversely, groups B and C showed a marked decrease in mtDNA content per cell when compared with uninfected individuals [54% and 60% of the control value (100%), respectively; P=0.001], as well as decreased absolute activity of COX (57% and 91% of the control value, respectively; P=0.07). Similar results were observed when mtDNA and COX activity were normalized by the mitochondrial amount (86% and 52% of the control value, respectively; P=NS, for normalized mtDNA content, and 72% and 66% of the control value, respectively; P=0.02, for normalized COX activity). We found a positive correlation between mtDNA content and COX activity (R²=0.3, P<0.001).

CONCLUSIONS: Decreased mtDNA content in AT of HIV-infected patients is closely associated with decreased COX activity, irrespective of the presence of HAART, before LD appears. The exact role that HIV itself and HAART play in adipocyte changes remains to be determined.

2004-10-25
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