Deveaud C, Beauvoit B, Rigoulet M; IAS Conference on HIV Pathogenesis and Treatment (2nd : 2003 : Paris, France).
Antivir Ther. 2003; 8 (Suppl.1): abstract no. 734.
Institut de Biochimie et de Genetique Cellulaires, Universite V. Segalen - CNRS, Bordeaux, France
Lipodystrophy, and specifically the loss of subcutaneous fat (lipoat-rophy) is a significant and distressing side effect of antiretroviral therapy. Nowadays, it is usually considered that NRTIs could have a role in LD development, via effects that have been ascribed to the induction of mitochondrial dysfunction of adipose tissue. The aims of this work was: (i) to compare mitochondrial metabolism representative parameters of superficial and deep adipose tissues from control rats; and (ii) to test whether NRTIs cause mitochondrial metabolism modifications in these two kinds of adipose tissues from rats treated with AZT compared with control rats. For the first set of experiments, we used inguinal (for superficial) and epididymal (for deep) adipose tissues from male Wistar rats free of treatment and for the second set of experiments, we treated Wistar male rats for 1 or 4 weeks with 70 mg AZT/kg/day, and extracted inguinal and epididymal adipose tissues from these rats, for further studies. First, we found that epididymal tissue was significatively enriched in respiratory chain complexes and citrate synthase-specific activities compared to inguinal adipose tissue. Also, it contained significatively more mtDNA per cell than inguinal tissue. Moreover, respiration was more elevated in epididymal adipocytes than in inguinal adipocytes. In the second part, we found that the specific activity of respiratory chain complexe IV and mtDNA concentration were significantly lower in superficial adipose tissue of AZT-treated rats as compared to control rats. In contrast, no significant difference was observed for deep adipose tissue. Our working hypothesis is that higher sensitivity of superficial adipose tissue towards NRTIs is linked to its lower mitochondrial enzymatic equipment. Metabolic consequences of this higher sensitivity of superficial adipose tissue are now under investigation.
Publication Types:
Keywords:
- Adipocytes
- Adipose Tissue
- Animals
- Cell Respiration
- Citrate (si)-Synthase
- DNA, Mitochondrial
- Electron Transport
- Electron Transport Complex IV
- Epididymis
- HIV-Associated Lipodystrophy Syndrome
- Lipodystrophy
- Male
- Mitochondria
- Rats
- Rats, Wistar
- Reverse Transcriptase Inhibitors
- Zidovudine
- metabolism
- physiology
- therapy
Other ID:
UI: 102263013
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