Introduction and Purpose HIV-infected patients on antiretroviral therapy have been reported to develop a lipodystrophy syndrome. Both HIV-1 protease inhibitors, as well as nucleoside analogue reverse transcriptase inhibitors, have been implicated. However, it is unclear if this is a direct drug effect or a result of an interaction between the drug and the underlying HIV infection. In order to dissect out the direct role of drug alone in this process, we studied the in vivo effect of a single protease inhibitor, indinavir, on the key adipogenic transcription factors C/EBPa, SREBP1c, and PPARg.
Methods We obtained abdominal subcutaneous adipose tissue samples from seven HIV-negative subjects at baseline and after 4 weeks of daily oral indinavir at 800 mg three times a day. Adipocytes were obtained by collagenase digestion, and total RNA was isolated by standard methods. Expression of C/EBPa, SREBP1c, and PPARg mRNA was quantitated by real time reverse transcription normalized to expression of b-actin using the delta Ct method.
Results The subjects had a mean age of 36 ± 3 years, with a mean BMI of 29.5 ± 9 kg/m2. There was no change in BMI or waist-to-hip ratio after 4 weeks of indinavir. Indinavir treatment had no effect on expression of C/EBPa (304.0 ± 32.3 vs 359. 2 ± 43.4), SREBP1c (82.0 ± 14.0 vs 104.9 ± 34.0), or PPARg (350.7 ± 54.0 vs 351.0 ± 48.8 relative units).
Conclusions Four weeks of the protease inhibitor indinavir does not alter adipogenic transcription factors in healthy HIV-negative subjects. Our findings indicate that indinavir does not appear to have a direct role in the development of lipodystrophy, suggesting that the lipodystrophy is likely either due to an interaction between drug and disease or attributable to antiretroviral agents other than indinavir.
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