title: Triglyceride-rich lipoprotein metabolism in unique VLDL receptor, LDL receptor, and LRP triple-deficient mice.
abstract: The very low density lipoprotein receptor (VLDLR), low density lipoprotein receptor (LDLR), and low density lipoprotein receptor-related protein (LRP) are the three main apolipoprotein E-recognizing endocytic receptors involved in the clearance of triglyceride (TG)-rich lipoproteins from plasma. Whereas LDLR deficiency in mice results in the accumulation of plasma LDL-sized lipoproteins, VLDLR or LRP deficiency alone only minimally affects plasma lipoproteins. To investigate the combined effect of the absence of these receptors on TG-rich lipoprotein levels, we have generated unique VLDLR, LDLR, and LRP triple-deficient mice. Compared with wild-type mice, these mice markedly accumulated plasma lipids and lipases. These mice did not show aggravated hyperlipidemia compared with LDLR and LRP double-deficient mice, but plasma TG was increased after high-fat diet feeding. In addition, these mice showed a severely decreased postprandial TG clearance typical of VLDLR-deficient (VLDLR-/-) mice. Collectively, although VLDLR deficiency in LRP- and LDLR-/- mice does not aggravate hyperlipidemia, these triple-deficient mice represent a unique model of markedly delayed TG clearance on a hyperlipidemic background.
authors.affiliation: Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands.
authors.forename: Sonia M S
authors.initials: SM
authors.lastname: Espirito Santo
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.forename: Jeltje R
authors.initials: JR
authors.lastname: Goudriaan
authors.forename: André
authors.initials: A
authors.lastname: Bensadoun
authors.forename: Niels
authors.initials: N
authors.lastname: Bovenschen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Bart J M
authors.initials: BJ
authors.lastname: van Vlijmen
mesh_terms: D000483:Alleles; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005838:Genotype; D006949:Hyperlipidemias / Q000473:pathology; D051756:Leucine-Responsive Regulatory Protein; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics* / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014280:Triglycerides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D008074:Lipoproteins; D011973:Receptors, LDL; D014157:Transcription Factors; D014280:Triglycerides; C036053:VLDL receptor; D051756:Leucine-Responsive Regulatory Protein; D002784:Cholesterol