Expression of adipogenic transcription factors, peroxisome proliferator-activated receptor gamma co-activator 1, IL-6 and CD45 in subcutaneous adipose tissue in lipodystrophy associated with highly active antiretroviral therapy

Objective: To determine the expressions of multiple genes in the subcutaneous adipose tissue of HIV-positive, highly active antiretroviral therapy (HAART)-treated patients with and without lipodystrophy. Design and methods: Real-time polymerase chain reaction was used to measure gene expressions in this cross-sectional study. Results: The messenger RNA concentrations of adipose transcription factors (peroxisome proliferator-activated receptor (PPAR) gamma and delta and sterol regulatory element binding protein 1 c) were all significantly lower in the lipodystrophic than the non-lipodystrophic group. The mRNA concentration of PPAR-gamma co-activator 1 (PGC-1), which regulates mitochondrial biogenesis, was lower in the lipodystrophic than the non-lipodystrophic group. The mRNA expression of lipoprotein lipase, acyl coenzyme A synthase and glucose transport protein 4 were significantly lower in the lipodystrophic than the non-lipodystrophic group, but the mRNA concentrations of fatty acid transport and binding proteins were similar in both groups. The mRNA concentrations of IL-6 and CD45 (a common leukocyte marker) were significantly higher in the lipodystrophic than the non-lipodystrophic group. Conclusion: Multiple alterations characterize gene expression in the subcutaneous adipose tissue of patients with HAART-associated lipodystrophy compared with HIV-positive, HAART-treated patients without lipodystrophy. The low expression of transcription factors inhibits adipocyte differentiation. The low expression of PGC-1 may contribute to mitochondrial defects. In addition, IL-6 and CD45 expressions are increased, the latter implying an excessive number of cells of leukocyte origin in lipodystrophic adipose tissue. Mitochondrial injury and an excess of proinflammatory cytokines may lead to increased apoptosis. All these changes may contribute to the loss of subcutaneous fat in HAART-associated lipodystrophy. (C) 2003 Lippincott Williams Wilkins.