Serum and hepatic nascent lipoproteins in normal and hypercholesterolemic rats

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 low fat chow diet in order to 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 imunoassayable apoB to apoE, and lipid composition, to hypercholesterolemic serum VLDL. Hepatic levels of LDL in hypercholesterolemic rats were markedly elevated and enriched in cholesteryl esters and apoE when compared 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.