Modulation of the plasma cholesteryl ester transfer by stachybotramide.

Plasma cholesteryl ester transfer protein (CETP), which mediates the transfer and exchange of neutral lipids (cholesteryl esters (CE) and triglycerides (TG) and phospholipids between plasma lipoproteins, plays an essential role in reverse cholesterol transport system. We have found that a fungal metabolite, stachybotramide, modulates the activity of CETP. Stachybotramide stimulated the [14C]CE transfer from high density lipoprotein (HDL) to very low density lipoprotein (VLDL) and low density lipoprotein (LDL) by 1.3- to 1.5-fold at 0.2-0.5 mM. This stimulation was abolished in the presence of anti-CETP antibody. On the other hand, the transfer of [14C]CE from LDL and VLDL to HDL was slightly reduced by stachybotramide at 0.5 mM. Unlike the transfer of [14C]CE, the transfer of [3H]TG from HDL was not significantly affected by stachybotramide. These results suggest that stachybotramide preferentially stimulate the CETP-mediated transfer of CE from HDL to both VLDL and LDL.