Aim: 

To analyze the molecular mechanisms that could be implicated in the changes of lipid and body fat composition associated to Efavirenz (EFV), the most recommended non-nucleoside reverse transcriptase inhibitor in HIV therapy.

Methods: 

Intracellular neutral lipids were studied by fluorescence microscopy (static cytometry) in Hep3B cells after 24h incubation with EFV (10, 25 or 50 mM). In order to define the nature of accumulated lipids, cells were treated for 4h with EFV (10 and 25 mM) and intracellular lipid content was determined by Nuclear Magnetic Resonance (NMR). Expression of the fatty acid transporters CD36 and FATP was analyzed by PCR after 4h incubation. Selected experiments were performed in cells pretreated (30 min) with the AMPK inhibitor Compound C (20mM).

Results: 

EFV induced neutral lipid accumulation in hepatic cells after 24h incubation. In NMR experiments (4h), the effects of EFV were also significantly evident. This alteration was not observed when fatty acids were removed from culture media, demonstrating that they were the result of fatty acid uptake from extracellular sources. Likewise, these changes did not occur in the presence of Compound C, pointing to a key role of AMPK in this lipid uptake. EFV also up-regulated CD36 and FATP mRNA expression.

Conclusion: 

EFV increases fatty acid uptake in Hep3B, leading to the accumulation of lipids. Given the long-term treatment of patients with EFV, this drug could alter lipid metabolism in the liver and be implicated in some of the alterations characteristic of lipodystrophy.