This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Use of protease inhibitor (PI)based highly active antiretroviral therapy (HAART) has been associated with altered regional fat distribution, insulin resistance, and dyslipidemias. To assess how PI-based HAART affects adipocyte gene expression in male HIV-1infected patients, reverse transcriptionpolymerase chain reaction was used to quantify messenger RNA expression of adipocyte transcription factors and adipocytokines in thigh and abdominal subcutaneous adipose tissue from male (1) HIV-1 seronegative subjects (control, n = 9), (2) asymptomatic treatment-naive HIV-1infected patients (naive, n = 6), (3) HIV-1infected patients who were receiving antiretroviral agents but never received PIs (PI naive, n = 5), (4) HIV-1infected patients who were receiving PI-based HAART (PI, n = 7), and (5) HIV-1infected patients who discontinued the PI component of their antiviral therapy more than 6 months before enrollment (past PI, n =7). In the PI group, the messenger RNA expression levels of the CCAAT/enhancerbinding protein , leptin, and adiponectin (18%, P < .01; 23%, P < .05; and 13%, P < .05, respectively) were significantly lower than the levels measured in the PI-naive group. These results are consistent with previous studies on the effects of PIs on cultured adipocytes. Prospective longitudinal studies of thigh fat adipose tissue gene expression could provide further insights on the pathogenesis of metabolic complications associated with PI-based HAART.
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