Abstract
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.
Highlights
Studieswere performed to determine the mechanism of hepatic removal of a cholesterol-rich@-migratinglipoprotein
This IDL has a mean particle diameter of 350 A and contains cholesteryl esters as its primary core lipid. It contains both apoBHand BL,apoE and C and, in addition, apoA-I. To differentiate this fraction from the IDL resulting from the metabolism of very low density lipoproteins (VLDL) in normocholesterolemic rats, we propose to designate the d 1.006-1.03 g/ml fraction of the cholesterol-fed diabetic rats as IDL
T h e removal was markedly decreased with over 80% of the administered radioactivity remaining in the plasma after 30 min
Summary
T h e removal was markedly decreased with over 80% of the administered radioactivity remaining in the plasma after 30 min These findings indicate that the liver is the primary site of removal of IDL,. In the hepatectomized rat 90% of the administered radioactivity was recovered in the plasma and this was due in part to the virtual absence of removal of apoBHand BLa, nd transfer of apoA-I and C-apoproteins to HDL. In the hepatectomized rats treated with estrogen, less apoA-I and C-apoproteins were recovered in the plasma, suggesting extrahepatic removal of these apoproteins. Livers from estradiol-treated rats were perfused and no augmentation of removal of IDL, was found, whereas the removal of human LDL and rat VLDL remnants was considerably increased (shown below).
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