Journal of Lipid Research, Vol 22, 971-989, Copyright © 1981 by Lipid Research, Inc.
Serum and hepatic nascent lipoproteins in normal and hypercholesterolemic rats
PJ Dolphin
The lipids and apoproteins of serum, hepatic Golgi cisternae, and secretory
vesicle lipoproteins from hypothyroid, hypercholesterolemic rats were
analyzed and compared to homologous lipoprotein fractions from euthyroid
rats fed a low fat chow diet in order tao determine the nature of the
nascent lipoprotein particles and indicate post-secretory modifications.
Normal rat hepatic Golgi and secretory vesicles contained predominantly
triglyceride-rich very low density lipoprotein (VLDL) which had little
associated apoC-II or C-III and was deficient in apoE when compared to
serum VLDL. Small quantities of cholesteryl ester-enriched low density
lipoprotein (LDL) containing apoB and apoE were also present. Hepatic
fractions from hypercholesterolemic rats contained cholesteryl ester- and
apoE-rich, triglyceride-depleted VLDL of similar size, immunodiffusion
characteristics, ratio of immunoassayable apoB to apoE, and lipid
composition, to hypercholesterolemic serum VLDL. Hepatic levels of LDL in
hypercholesterolemic rats were markedly elevated and enriched in
cholesteryl ester and apoE when compare to normal hepatic LDL. Cholesteryl
ester-rich hepatic VLDL and LDL increased in size and in cholesteryl ester
and apoE content during transit from the Golgi cisternae into the secretory
vesicles. Triglyceride-rich VLDL only acquired apoE which was further
supplemented upon secretion. Nascent VLDL and LDL represented LpB-LpE
association complexes and no deficiency in any apoE isoprotein within the
cholesteryl ester-rich serum lipoproteins was observed. Thus,
dietary-induced hypercholesterolemia in hypothyroid rats results in a fatty
liver whose lipoprotein secretory products contribute to the plasma pool of
abnormal cholesteryl ester- and apoE-enriched lipoproteins.