Role of FAP48 in HIV-associated lipodystrophy.
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.
Third Division Cotugno Hospital, Naples, Italy. esposvin@libero.it
Vincenzo
V
Esposito
Lucrezia
L
Manente
Angela
A
Lucariello
Angelica
A
Perna
Rosaria
R
Viglietti
Miriam
M
Gargiulo
Roberto
R
Parrella
Giovanni
G
Parrella
Alfonso
A
Baldi
Antonio
A
De Luca
Antonio
A
Chirianni
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000480:Alkynes; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D048588:Benzoxazines / Q000009:adverse effects / Q000494:pharmacology; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D002219:Carbamates / Q000009:adverse effects / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003521:Cyclopropanes; D005663:Furans; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D019469:Indinavir / Q000009:adverse effects / Q000494:pharmacology; D051379:Mice; D019258:Saquinavir / Q000009:adverse effects / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D018119:Stavudine / Q000009:adverse effects / Q000494:pharmacology; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000480:Alkynes; D048588:Benzoxazines; D002219:Carbamates; D003521:Cyclopropanes; D005663:Furans; C103024:GLMN protein, human; D005938:Glucocorticoids; D013449:Sulfonamides; C095108:amprenavir; D019469:Indinavir; D018119:Stavudine; D019703:Calcineurin; C098320:efavirenz; D019258:Saquinavir