HIV protease inhibitors block adipocyte differentiation independently of lamin A/C.
OBJECTIVE
To determine the importance of lamin A/C for fat cell differentiation in vitro and for the anti-adipogenic activity of HIV protease inhibitors such as indinavir.


METHODS
Lipodystrophy-associated and processing-defective mutants of lamin A were stably expressed at high levels in 3T3-L1 pre-adipocytes. Additionally, 3T3-L1 pre-adipocytes with stable reduction of lamin A/C or emerin were derived. The cells were differentiated for 8 days into mature adipocytes in the presence or absence of indinavir or nelfinavir.


RESULTS
3T3-L1 cells stably expressing high levels of lipodystrophy-associated or processing-defective mutants of lamin A differentiated with comparable efficiencies to control cells. Similarly, cells with dramatically reduced lamin A levels differentiated as efficiently as controls. Although indinavir stimulated the accumulation of unprocessed lamin A, cells with dramatically reduced lamin A/C levels and no detectable prelamin A remained responsive to an indinavir-induced inhibition of adipogenesis.


CONCLUSIONS
The ability of HIV protease inhibitor to stimulate the accumulation of unprocessed lamin A is neither necessary nor sufficient to explain their anti-adipogenic activity. Furthermore, lamin A/C plays a minimal role in the differentiation of 3T3-L1.
Kudlow
Brian A
BA
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Jameson
Samantha A
SA
Kennedy
Brian K
BK
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D005822:Genetic Vectors; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019469:Indinavir / Q000494:pharmacology; D034904:Lamin Type A / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D013946:Thymopoietins / Q000502:physiology
D017320:HIV Protease Inhibitors; D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011498:Protein Precursors; D034741:RNA, Small Interfering; D013946:Thymopoietins; C092710:emerin; C440308:lamin C; C090764:prelamin A; D019469:Indinavir