Ethanol-Induced Redistribution of Cholesteryl Ester Transfer Protein (CETP) Between Lipoproteins

Abstract

Abstract Since alcohol drinking reduces the concentration and activity of plasma cholesteryl ester transfer protein (CETP), we investigated the effects of alcohol on its synthesis and secretion by perfusing rabbit livers for 4 hours in the absence or presence of ethanol. The quantity of CETP mRNA in the perfused livers did not differ between the control and ethanol (25 mmol/L or 50 mmol/L) perfusions. CETP activity was determined by incubating [ 3 H]cholesteryl ester–labeled human LDL and unlabeled human HDL with the perfusion medium after removing the endogenous VLDL (secreted by the perfused liver) by ultracentrifugation. CETP activity in the perfusion medium increased at a linear rate that was not affected by ethanol. When the VLDL was removed by precipitation with polyethylene glycol or a heparin-Sepharose column instead of ultracentrifugation, practically no CETP activity was detected in the ethanol perfusions, whereas these procedures did not affect CETP activity in the control perfusions. Inhibition of ethanol oxidation by 4-methylpyrazole resulted in CETP activity similar to that of the controls. We conclude that ethanol does not affect the synthesis or secretion of CETP, but its oxidation may alter the distribution of CETP in lipoproteins. CETP seems to be present in VLDL as well as in HDL, and since VLDL is more rapidly catabolized than HDL, this may explain the low plasma CETP concentration associated with alcohol consumption.