Nascent hepatic lipoproteins in hypothyroid rats

Cholesterol-feeding of hypothyroid Long-Evans rats results in a marked hypercholesterolemia and hepatic secretion of cholesteryl ester and apoE-rich VLDL and LDL which accumulate in the serum compartment (J. Lipid Res. 1981 22: 971-989). The present study segregates the effects of hypothyroidism from the combined effects reported above. Hypothyroidism alone does not result in the secretion of cholesteryl ester-rich lipoproteins by the liver which, in contrast, contains depressed quantities (30%) of triglyceride-rich (71% of lipid mass) VLDL and low levels of LDL which is also triglyceride-rich when compared to the nascent lipoproteins of euthyroid rat livers. The nascent lipoproteins from the hepatic Golgi cisternae and secretory vesicles of hypothyroid rats all had pre-beta or slow pre-beta migration on agarose gel electrophoresis and were very dissimilar in lipid and apoprotein composition from the beta-migrating LDL that accumulates in the sera of these animals and contains 13.8% triglyceride, 51.3% cholesteryl ester, and has an apoB/apoE ratio of 32.7. We conclude that the serum LDL in hypothyroid rats, which contains only apoB100, is not secreted directly by the liver but represents a normal catabolite of triglyceride-rich VLDL that may accumulate due to reduced receptor-mediated clearance rather than an overproduction of its immediate precursor, hepatic VLDL.