CENTRIPETAL CHOLESTEROL FLUX TO THE LIVER IS DICTATED BY EVENTS IN THE PERIPHERAL ORGANS AND NOT BY THE PLASMA HIGH-DENSITY-LIPOPROTEIN OR APOLIPOPROTEIN-A-I CONCENTRATION

The major net flux of cholesterol in the intact animal or human is fro m the peripheral organs to the liver, This flux is made up of choleste rol that is either synthesized in these peripheral tissues or taken up as lipoprotein cholesterol, This study investigates whether it is the concentration of apolipoprotein (apo) A-I or high density lipoprotein in the plasma that determines the magnitude of this flux or, alternat ively, whether events within the peripheral cells themselves regulate this important process. In mice that lack apoA-I and have very low con centrations of circulating high density lipoprotein, it was found that there was no accumulation of cholesterol in any peripheral organ so t hat the mean sterol concentration in these tissues was the same (2208 +/- 29 mg/kg body weight) as in control mice (2176 +/- 50 mg/kg), Furt hermore, by measuring the rates of net cholesterol acquisition in the peripheral organs from de novo synthesis and uptake of low density lip oprotein, it was demonstrated that the magnitude of centripetal sterol movement from the peripheral organs to the liver was virtually identi cal in control animals (78 +/- 5 mg/day per kg) and in those lacking a poA-I (72 +/- 4 mg/day per kg).jlr These studies indicate that the mag nitude of net sterol flux through the body is not related to the conce ntration of high density lipoprotein or apolipoprotein A-I in the plas ma, but is probably determined by intracellular processes in the perip heral organs that dictate the rate of movement of cholesterol from the endoplasmic reticulum to the plasma membrane.