saquinavir and HIV-Associated-Lipodystrophy-Syndrome

The highly active antiretroviral therapy (HAART) can cause a metabolic syndrome consisting of lipodystropy/lipoatrophy, dyslipidemia, and type 2 diabetes mellitus with an increased cardiovascular risk. The pathogenetic bases of HAART-associated lipodystrophy are poorly known. A genetic screen was used to evaluate proteins that are modulated in HIV-1-infected patients with or without lipodystrophy syndrome, that are routinely treated with HAART regimens. The most significant modulation was represented by FAP48 expression. Stable over-expression of FAP48 was able to alter, in vitro, adipogenesis, acting both on calcineurin and glucocorticoid pathways. Finally, we demonstrated that FAP48 over-expression was able to influence the capacity of some HIV drugs, Saquinavir and Efavirenz, but not Stavudine, Amprenavir, and Indinavir to inhibit adipocyte formation. In conclusion, this molecule could be a potential target for novel therapeutic approaches to the HAART related lipodystrophy in HIV patients.

Topics: Adaptor Proteins, Signal Transducing; Adipocytes; Alkynes; Animals; Antiretroviral Therapy, Highly Active; Benzoxazines; Calcineurin; Carbamates; Cell Differentiation; Cell Line; Cyclopropanes; Furans; Gene Expression; Glucocorticoids; HIV-1; HIV-Associated Lipodystrophy Syndrome; Humans; Indinavir; Mice; Saquinavir; Signal Transduction; Stavudine; Sulfonamides; Transfection