Role of FAP48 in HIV-associated lipodystrophy

J Cell Biochem. 2012 Nov;113(11):3446-54. doi: 10.1002/jcb.24221.

Abstract

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Alkynes
  • Animals
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Benzoxazines / adverse effects
  • Benzoxazines / pharmacology
  • Calcineurin / genetics
  • Calcineurin / metabolism
  • Carbamates / adverse effects
  • Carbamates / pharmacology
  • Cell Differentiation / drug effects
  • Cell Line
  • Cyclopropanes
  • Furans
  • Gene Expression / drug effects
  • Glucocorticoids / metabolism
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • HIV-Associated Lipodystrophy Syndrome / chemically induced
  • HIV-Associated Lipodystrophy Syndrome / metabolism*
  • Humans
  • Indinavir / adverse effects
  • Indinavir / pharmacology
  • Mice
  • Saquinavir / adverse effects
  • Saquinavir / pharmacology
  • Signal Transduction / drug effects
  • Stavudine / adverse effects
  • Stavudine / pharmacology
  • Sulfonamides / adverse effects
  • Sulfonamides / pharmacology
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • Alkynes
  • Benzoxazines
  • Carbamates
  • Cyclopropanes
  • Furans
  • GLMN protein, human
  • Glucocorticoids
  • Sulfonamides
  • amprenavir
  • Indinavir
  • Stavudine
  • Calcineurin
  • efavirenz
  • Saquinavir