Effects of apolipoprotein B-100 on the metabolism of a lipid microemulsionmodel in rats

In previous studies, it was shown that lipid microemulsions resembling LDL (LDE) but not containing protein, acquire apolipoprotein E when injected in to the bloodstream and bind to LDL receptors (LDLR) using this protein as l igand. Aiming to evaluate the effects of apolipoprotein (apo) B-100 on the catabolism of these microemulsions, LDE with incorporated apo B-100 (LDE-ap oB) and native LDL, all labeled with radioactive lipids were studied after intraarterial injection into Wistar rats. Plasma decay curves of the labels were determined in samples collected over 10 h and tissue uptake was assay ed from organs excised from the animals sacrificed 24 h after injection. LD E-apo B had a fractional clearance rate (FCR) similar to native LDL (0.40 a nd 0.33, respectively) but both had FCR pronouncedly smaller than LDE (0.56 , P<0.01). Liver was the main uptake site for LDE, LDE-apoB, and native LDL , but LDE-apoB and native LDL had lower hepatic uptake rates than LDE. Pre- treatment of the rats with 17 alpha-ethinylestradiol, known to upregulate L DLR, accelerated the removal from plasma of both LDE and LDE-apoB, but the effect was greater upon LDE than LDE-apoB. These differences in metabolic b ehavior documented in vivo can be interpreted by the lower affinity of LDLR for apo B-100 than for apo E, demonstrated in in vitro studies. Therefore, our study shows in vivo that, in comparison with apo E, apo B is a less ef ficient ligand to remove lipid particles such as microemulsions or lipoprot eins from the intravascular compartment. (C) 1999 Elsevier Science B.V. All rights reserved.