Secretion of Lipoproteins from the Liver of Normal and Watanabe Heritable Hyperlipidemic Rabbits

• Published in: Proceedings of the National Academy of Sciences - PNAS 1983-10, Vol.80 (19), p.6096-6100
• Main Authors: Hornick, Conrad A., Kita, Toru, Hamilton, Robert L., Kane, John P., Havel, Richard J.
• Format: Article
• Language: English
• Subjects: Animals; Apolipoproteins - biosynthesis; Blood plasma; Cholesterol - blood; Cholesterol - metabolism; Cholesterol esters; Cholesterols; Hyperlipidemias - metabolism; IDL lipoproteins; Kinetics; Lipids; Lipoproteins; Lipoproteins - blood; Lipoproteins - metabolism; Liver; Liver - metabolism; Male; Perfusion; Phospholipids - metabolism; Rabbits; Reference Values; Secretion; Triglycerides; Triglycerides - blood; Triglycerides - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.80.19.6096

We compared the rate of accumulation of lipoproteins in perfusates of isolated livers from normal New Zealand White rabbits and Watanabe heritable hyperlipidemic (WHHL) rabbits, in which a gene mutation has produced a virtually complete deficiency of low density lipoprotein (LDL) receptors. The rate of accumulation of apolipoprotein B-100 did not differ in perfusates of livers from normal and mutant animals and little or no apolipoprotein B-48 was detected. In both groups, virtually all apolipoprotein B accumulated in very low density lipoprotein (VLDL). Experiments in which [3H]lysine was added to the perfusates showed that the apolipoprotein B that accumulated in VLDL was newly synthesized by the liver whereas the small amount of apolipoprotein B found in lipoproteins of higher density appeared to be washed out of extravascular spaces during perfusion. Perfusate VLDL from both groups contained more triglycerides and less cholesteryl esters than their counterparts from blood plasma. As compared with perfusate VLDL from normal livers, those from livers of WHHL rabbits were enriched in cholesteryl esters. Experiments in which Triton WR-1339 was injected into the blood of intact rabbits confirmed the observations with perfused livers. Previous studies have shown that the extent to which VLDL is converted to LDL is increased several-fold in WHHL rabbits. Taken together with our present results, which fail to provide evidence for increased secretion of apolipoprotein B or de novo secretion of lipoproteins other than VLDL that contain apolipoprotein B, it can be concluded that overproduction of LDL in rabbits lacking LDL receptors is solely the result of altered metabolism of VLDL.