Title
The hepatic uptake of VLDL in lrp-ldlr-/-vldlr-/- mice is regulated by LPL activity and involves proteoglycans and SR-BI
Author
TNO Kwaliteit van Leven
Hu, L.
van der Hoogt, C.C.
Espirito Santo, S.M.S.
Out, R.
Kypreos, K.E.
van Vlijmen, B.J.M.
van Berkel, T.J.C.
Romijn, J.A.
Havekes, L.M.
van Dijk, K.W.
Rensen, P.C.N.
Publication year
2008
Abstract
LPL activity plays an important role in preceding the VLDL remnant clearance via the three major apolipoprotein E (apoE)-recognizing receptors: the LDL receptor (LDLr), LDL receptor-related protein (LRP), and VLDL receptor (VLDLr). The aim of this study was to determine whether LPL activity is also important for VLDL remnant clearance irrespective of these receptors and to determine the mechanisms involved in the hepatic remnant uptake. Administration of an adenovirus expressing LPL (AdLPL) into lrp-ldlr-/-vldlr-/- mice reduced both VLDL-triglyceride (TG) and VLDL-total cholesterol (TC) levels. Conversely, inhibition of LPL by AdAPOC1 increased plasma VLDL-TG and VLDL-TC levels. Metabolic studies with radiolabeled VLDL-like emulsion particles showed that the clearance and hepatic association of their remnants positively correlated with LPL activity. This hepatic association was independent of the bridging function of LPL and HL, since heparin did not reduce the liver association. In vitro studies demonstrated that VLDL-like emulsion particles avidly bound to the cell surface of primary hepatocytes from lrp-ldlr-/-vldlr-/- mice, followed by slow internalization, and involved heparin-releaseable cell surface proteins as well as scavenger receptor class B type I (SR-BI). Collectively, we conclude that hepatic VLDL remnant uptake in the absence of the three classical apoE-recognizing receptors is regulated by LPL activity and involves heparan sulfate proteoglycans and SR-BI. Copyright © 2008 by the American Society for Biochemistry and Molecular Biology, Inc.
Subject
Healthy Living
Healthy for Life
Apolipoprotein
Denovirus-mediated gene transfer
Lipoprotein lipase
Low density lipoprotein receptor
Low density lipoprotein receptor-related protein
Transgenic mice
Triglyceride-rich emulsion particles
Very low density lipoprotein receptor
apolipoprotein E
cell surface protein
cholesterol
low density lipoprotein receptor
low density lipoprotein receptor related protein
proteoglycan
proteoheparan sulfate
scavenger receptor BI
triacylglycerol
very low density lipoprotein
very low density lipoprotein receptor
CD36 antigen
ligand
very low density lipoprotein cholesterol
Adenovirus
animal cell
animal experiment
animal tissue
cell isolation
cell surface
controlled study
enzyme activity
in vitro study
in vivo study
internalization
lipid analysis
liver cell
mouse
nonhuman
protein expression
regulatory mechanism
animal
blood
emulsion
genetics
metabolism
mouse mutant
Animals
Antigens, CD36
Cholesterol, VLDL
Emulsions
LDL-Receptor Related Proteins
Ligands
Lipoprotein Lipase
Liver
Male
Mice
Mice, Knockout
Proteoglycans
Receptors, LDL
To reference this document use:
http://resolver.tudelft.nl/uuid:2703c7b0-22e4-4052-952d-ce70fc8f42a8
DOI
https://doi.org/10.1194/jlr.m800130-jlr200
TNO identifier
241187
ISSN
0022-2275
Source
Journal of Lipid Research, 49 (49), 1553-1561
Document type
article