The hepatic uptake of rat high-density lipoprotein cholesteryl ester is delayed after treatment with cholesteryl ester transfer protein

The effects of cholesteryl ester transfer protein (CETP) on the direct upta ke of HDL cholesteryl ester by the liver was investigated using the rat in vivo and the isolated perfused rat liver as experimental models, Rat plasma was incubated with [H-3]cholesterol in the presence or absence of partiall y purified human CETP far 18 hr and [H-3]cholesteryl ester-labeled HDL was then isolated by ultracentrifugation, The CETP-treated as compared to untre ated HDL showed a small shift toward a lower density in the peak of lipopro tein cholesterol, suggesting that the HDL particle size was increased, Afte r injection of the labeled HDL into rats in vivo, more radioactivity remain ed in the plasma after 60 min when the CETP-treated preparation was used, b ut the amounts found in the liver and secreted in the bile were not signifi cantly different from those obtained with the untreated HDL, The distributi on of the label remaining in the plasma after 60 min between different dens ity fractions corresponding to HDL subclasses suggested that the uptake of HDL, and HDL, was delayed by CETP treatment. Radioactivity from CETP-treate d HDL was also removed from the perfusate of isolated perfused rat livers m ore slowly than that from untreated HDL, and in this case the amount found in the liver after 60 min was significantly lower, These findings indicate that treatment with CETP has a direct inhibitory effect on the clearance of rat HDL cholesteryl ester from the blood and its uptake by the liver.