758 Impaired Gene Expression in Adipose Tissue of HIV Subjects Undergoing HAART, Affected by Severe Lipodystrophy A. Napolitano*, I. Marchetti, R. Guttmann, P. Ferrari, J. L. Sadoul, P. Dellamonica, J. Durant CHU Archet, Nice, France
Background: Lipodystrophy and severe metabolic disturbances such as dyslipidemia and diabetes are a major side effect seen in HIV subjects under HAART. These changes could potentially lead to increased cardiovascular risk and, it seems, that not only protease inhibitors could be responsible for this new syndrome. Therefore, we analyzed adipocyte specific gene expression in a group of subjects affected from severe lipodystrophy to test whether HAART could play a tissue specific role in adipose tissue dysfunction at the molecular level.
Methods: Gluteal and periombelical subcutaneous adipose tissue biopsies were performed on 11 subjects (M/F)(10/1) presenting with severe lipodystrophy (HAART > 24 months (mos), HIV-RNA < 40 copies/ml, CD4 560 +/-177mm3). Metabolic assessments (Triglycerides, ApoE , BG, insulin and leptin were performed. At the time of the study all subjects have been under at least one NRTI and/or one NNRTI but only 3 were under PI for at least 6 mos. Real-time PCR using Taqman probes have been performed for LPL, leptin, Glut4, PPARgamma, and SREBP1 normalized to P0 on adipose tissue cDNA of lipodystrophic subjects compared to 8 controls. Results are expressed as a ratio (I-CYCLER Real Time Detection System software).
Results: Glut4, PPARg, and SREBP1 mRNA were dramatically reduced in HIV subjects vs controls Glut4/P0 0.001 +/-0 vs 4.93 +/-2.015 , PPARg/P0 0.001 +/-0 vs1.719 +/-0.701, SREBP1/P0 1.41 +/-0.393 vs 2.58 +/-1.053) while LPL and leptin gene expression present a less striking reduction ( LPL/P0 0.3488 +/-0.097 vs 1.35 +/-0.551, leptin/P0 0.346 +/-0.25 vs 1.52 +/-0.62). All subjects present hypertriglyceridemia ( 5.28 +/-1.76 mmol/L ) and moderate insulin resistance (BG 6.25 +/-1.8 mmol/L, insulin 8.66 +/-2.6 mU/I). Serum leptin levels were reduced (6.24 +/-1.88 ng/ml), while ApoE was increased (125.5 +/-41.8 mg/L).
Conclusions: There are drastic reductions in some and more modest reductions in other adipocyte specific gene expression in HIV subjects undergoing HAART. These reductions in adipocyte gene expression are not simply caused exclusively by PI treatment, as subjects undergoing only NRTI and/or NNRTI treatment display similar changes in absence of PI therapy.
