Print Email Facebook Twitter The hepatic uptake of VLDL in lrp-ldlr-/-vldlr-/- mice is regulated by LPL activity and involves proteoglycans and SR-BI Title The hepatic uptake of VLDL in lrp-ldlr-/-vldlr-/- mice is regulated by LPL activity and involves proteoglycans and SR-BI Author 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. TNO Kwaliteit van Leven 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 for LifeBiologyHealthy LivingApolipoproteinDenovirus-mediated gene transferLipoprotein lipaseLow density lipoprotein receptorLow density lipoprotein receptor-related proteinTransgenic miceTriglyceride-rich emulsion particlesVery low density lipoprotein receptorapolipoprotein Ecell surface proteincholesterollipoprotein lipaselow density lipoprotein receptorlow density lipoprotein receptor related proteinproteoglycanproteoheparan sulfatescavenger receptor BItriacylglycerolvery low density lipoproteinvery low density lipoprotein receptorCD36 antigenligandvery low density lipoprotein cholesterolAdenovirusanimal cellanimal experimentanimal tissuearticlecell isolationcell surfacecontrolled studyenzyme activityin vitro studyin vivo studyinternalizationlipid analysisliver cellmalemousenonhumanpriority journalprotein expressionregulatory mechanismanimalbloodemulsiongeneticslivermetabolismmouse mutantAnimalsAntigens, CD36Cholesterol, VLDLEmulsionsLDL-Receptor Related ProteinsLigandsLipoprotein LipaseLiverMaleMiceMice, KnockoutProteoglycansReceptors, 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 (7), 1553-1561 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.