This study was designed to investigate the molecular effects of diphenyl diselenide ((PhSe)2) on cholesterol
metabolism in HepG2 cell line in a dose-dependent manner. The protein levels of both total and phosphorylated 3-
hydroxy-3-methylglutaryl coenzyme A reductase (HMGR and P-HMGR), low-density lipoprotein receptors (LDLr) and
the proteins involved in their regulatory network were analyzed by Western blotting, and the effect of (PhSe)2 on HMGR
activity was measured. Additionally, we also evaluated the effects of this compound on glucose transporter type 4
(GLUT4) translocation using fluorescence microscopy in L6 skeletal muscle cell line.
Results demonstrated that (PhSe)2 increased P-HMGR, HMGR, and LDLr protein levels as well as simvastatin treatment,
which was used as positive control, without directly affecting HMGR activity. We observed that both long- and short-term
HMGR regulation mechanisms are involved in the effects of (PhSe)2, as this compound was able to augment Sterol regulatory
element binding proteins (SREBP)-1 and Insulin induced gene (Insig)1 protein levels, and to increase AMP activated
kinase (AMPK) activation state. We also found that, in L6 skeletal myotubes, 10 μM (PhSe)2 increases GLUT4
translocation through AMPK activation.
Taken together, these findings suggest that (PhSe)2 can modulate the expression of some proteins involved in cholesterol
and glucose cell metabolism.