Receptor and non-receptor mediated uptake of chylomicron remnants by the liver.
The uptake of chylomicron remnants by rodent liver is mediated by proteins residing on the microvillous surface of hepatocytes and occurs in two steps. First, initial removal of the remnants from the blood occurs through binding to the low density lipoprotein (LDL) receptor via apo E and to hepatic lipase via polar lipids and proteins on the remnant surface. Second, chylomicron remnants are taken up into the cell mainly by the LDL receptor and follow the classical receptor-mediated pathway of endocytosis. The LDL receptor-related protein (LRP), which binds weakly to chylomicron remnants via apo E, does not appear to have a significant role in the initial removal process. The remnant particles can, however, be enriched with proteoglycan-bound apo E present on hepatocytic microvilli, which increases their affinity for LRP to the extent that they are subject to endocytosis by this receptor, particularly when the LDL receptor is deficient or down-regulated. Hepatic lipase can also mediate binding of remnants to LRP, for which it has high affinity. Lipolysis of remnant lipids by hepatic lipase may promote but is not required for interaction of remnants with the endocytic receptors. Proteoglycan-bound hepatic lipase may also mediate endocytosis of chylomicron remnants independent of apo E, so that hepatic catabolism of these particles is not completely dependent upon this apoprotein. Available data from experiments in vivo thus indicate redundancy of both steps of hepatic uptake of chylomicron remnants, consistent with the centrality of this process in nutrient delivery.
Havel
R J
RJ
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D001692:Biological Transport; D002914:Chylomicrons / Q000378:metabolism*; D006801:Humans; D008066:Lipolysis; D008099:Liver / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000378:metabolism*
D001057:Apolipoproteins E; D002914:Chylomicrons; D018110:Receptors, Lipoprotein; C028203:chylomicron receptor