Removal of lipid-rich lipoproteins by the liver

Studies were performed to determine the mechanism of hepatic removal of a cholesterol-rich beta-migrating lipoprotein. This fraction, designated IDLc, was isolated from the serum of cholesterol-fed diabetic rats by ultracentrifugation at d 1.006-1.03 g/ml and contained apoproteins B, E, C, and A-I. When 125I-IDLc (125I-labeled IDLc) was injected into normal chow-fed rats, 40% of the radioactivity was cleared from the plasma within 5 minutes with slight additional removal during the next 25 minutes. The rapid removal phase was due to the clearance of apoB-containing lipoproteins. The slow removal phase was due to transfer of apoA-I and C-apoproteins to HDL which has a considerably slower rate of turnover. The in vivo clearance of total 125I-IDLc radioactivity was enhanced by pretreatment of normal rats with 17 alpha-ethinyl estradiol. This appeared to be associated with lack of transfer of apoA-I and C-apoproteins to HDL, and the removal of these apoproteins along with the apoB-containing lipoproteins. Treatment of rats with 17 alpha-ethinyl estradiol did not result in an increased rate of removal of 125I-IDLc when their livers were perfused and this suggests that the removal of IDLc is not mediated by the LDL (B, E) receptor whose activity is stimulated by estradiol administration.