ETHANOL-INDUCED REDISTRIBUTION OF CHOLESTERYL ESTER TRANSFER PROTEIN (CETP) BETWEEN LIPOPROTEINS

Since alcohol drinking reduces the concentration and activity of plasm a cholesteryl ester transfer protein (CETP), we investigated the effec ts of alcohol on its synthesis and secretion by perfusing rabbit liver s for 4 hours in the absence or presence of ethanol. The quantity of C ETP mRNA in the perfused livers did not differ between the control and ethanol (25 mmol/L or 50 mmol/L) perfusions. CETP activity was determ ined by incubating [H-3]cholesteryl ester-labeled human LDL and unlabe led human HDL with the perfusion medium after removing the endogenous VLDL (secreted by the perfused liver) by ultracentrifugation. CETP act ivity in the perfusion medium increased at a linear rate that was not affected by ethanol. When the VLDL was removed by precipitation with p olyethylene glycol or a heparin-Sepharose column instead of ultracentr ifugation, practically no CETP activity was detected in the ethanol pe rfusions, whereas these procedures did not affect CETP activity in the control perfusions. Inhibition of ethanol oxidation by 4-methylpyrazo le resulted in CETP activity similar to that of the controls. We concl ude that ethanol does not affect the synthesis or secretion of CETP, b ut its oxidation may alter the distribution of CETP in lipoproteins. C ETP seems to be present in VLDL as well as in HDL, and since VLDL is m ore rapidly catabolized than HDL, this may explain the low plasma CETP concentration associated with alcohol consumption.