Effect of Rosiglitazone on Peroxisome Proliferator- Activated Receptor Gene Expression in Human Adipose Tissue Is Limited by Antiretroviral

(See the editorial commentary by Hadigan, on pages 1729–31.) Background. Treatment of human immunodeficiency virus (HIV)–1 with thymidine-analogue nucleoside reverse-transcriptase inhibitors (tNRTIs) causes lipoatrophy, mitochondrial toxicity, and lower adipose tissue expres-sion of peroxisome proliferator-activated receptor (PPAR [PPARG gene]). Rosiglitazone (RSG), a PPAR agonist, improves congenital lipoatrophy but not HIV lipoatrophy. Methods. Serial fat biopsies were taken from HIV-infected, lipoatrophic men randomized to receive RSG or placebo for 48 weeks. Adipose tissue mitochondrial and nuclear gene expression and mitochondrial DNA content were quantified by real-time polymerase chain reaction. Nonparametric analyses were applied. Results. Subjects receiving tNRTI-containing antiretroviral therapy had lower baseline mitochondrial RNA ex-pression and DNA content. In subjects receiving tNRTIs, exposure to RSG did not affect PPARG expression at either week 2 or 48. At week 2, RSG increased PPARG expression only in subjects not treated with tNRTIs, whereas at week 48, increased PPARG expression was observed in subjects not treated with tNRTIs, regardless of RSG use. Similar findings were observed for the PPARG-responsive gene fatty acid – binding protein 4. Changes in PPARG expression were associated with increases in limb fat mass. Conclusions. These data suggest that in HIV-infected, lipoatrophic men, adipose PPARG expression and func