CENTRIPETAL CHOLESTEROL FLUX FROM EXTRAHEPATIC ORGANS TO THE LIVER ISINDEPENDENT OF THE CONCENTRATION OF HIGH-DENSITY LIPOPROTEIN-CHOLESTEROL IN PLASMA

High density lipoproteins (HDLs) play a role in two processes that inc lude the amelioration of atheroma formation acid the centripetal flow of cholesterol from the extrahepatic organs to the liver. This study t ests the hypothesis that the flow of sterol from the peripheral organs to the liver is dependent upon circulating HDL concentrations. Transg enic C57BL/6 mice were used that expressed variable amounts of simian cholesteryl ester-transfer protein (CETP). The rate of centripetal cho lesterol flux was quantitated as the sum of the rates of cholesterol s ynthesis and low density lipoprotein-cholesterol uptake in the extrahe patic tissues. Steady-state concentrations of cholesterol carried in H DL (HDLC) varied from 59 to 15 mg/dl and those of apolipoprotein AI fr om 138 to 65 mg/dl between the control mice (CETP(c)) and those maxima lly expressing the transfer protein (CETP(+)). There was no difference in the size of the extrahepatic cholesterol pools in the CETP(c) and CETP(+) animals. Similarly, the rates of cholesterol synthesis (83 and 80 mg/day per kg, respectively) and cholesterol carried in Low densit y lipoprotein uptake (4 and 3 mg/day per hg, respectively) were virtua lly identical in the two groups. Thus, under circumstances where the s teady-state concentration of HDL-C varied 4-fold, the centripetal flux of cholesterol from the peripheral organs to the liver was essentiall y constant at approximate to 87 mg/day per kg. These studies demonstra te that neither the concentration of HDL-C or apolipoprotein AI nor th e level of CETP activity dictates the magnitude of centripetal cholest erol flux from the extrahepatic organs to the liver, at least in the m ouse.