HIV protease inhibitors block adipocyte differentiation independently of lamin A/C

AIDS. 2005 Oct 14;19(15):1565-73. doi: 10.1097/01.aids.0000186827.91408.90.


Objectives: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipogenesis / drug effects
  • Adipogenesis / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Nucleus / physiology
  • Cells, Cultured
  • Genetic Vectors
  • HIV Protease Inhibitors / pharmacology*
  • HIV-Associated Lipodystrophy Syndrome / genetics*
  • HIV-Associated Lipodystrophy Syndrome / pathology
  • Humans
  • Indinavir / pharmacology
  • Lamin Type A / genetics
  • Lamin Type A / physiology*
  • Membrane Proteins / physiology
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • Protein Precursors / genetics
  • Protein Precursors / physiology
  • RNA, Small Interfering / genetics
  • Thymopoietins / physiology


  • HIV Protease Inhibitors
  • Lamin Type A
  • Membrane Proteins
  • Nuclear Proteins
  • Protein Precursors
  • RNA, Small Interfering
  • Thymopoietins
  • emerin
  • lamin C
  • prelamin A
  • Indinavir