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Triglyceride-rich lipoprotein metabolism in unique VLDL receptor, LDL receptor, and LRP triple-deficient mice

Author: Espirito Santo, S.M.S. · Rensen, P.C.N. · Goudriaan, J.R. · Bensadoun, A. · Bovenschen, N. · Voshol, P.J. · Havekes, L.M. · Vlijmen, B.J.M. van
Type:article
Date:2005
Institution: TNO Kwaliteit van Leven
Source:Journal of Lipid Research, 6, 46, 1097-1102
Identifier: 238938
doi: doi:10.1194/jlr.C500007-JLR200
Keywords: Biology · Biomedical Research · Apolipoprotein E · Hepatic lipase · Hyperlipidemia · Lipoprotein lipase · Low density lipoprotein receptor · Postprandial response · Transgenic mice · Very low density lipoprotein receptor · Very low density lipoproteins · Lipid · Low density lipoprotein receptor · Low density lipoprotein receptor related protein · Triacylglycerol lipase · Very low density lipoprotein receptor · Leucine responsive regulatory protein · Lipoprotein · Transcription factor · Animal experiment · Animal model · Animal tissue · Controlled study · Female · gene deletion · Hyperlipidemia · Lipid blood level · Lipid diet · Male · Mouse · Nonhuman · Protein defect · Species comparison · Triacylglycerol blood level · Triacylglycerol lipase blood level · Wild type · Chemistry · Genetics · Metabolism · Pathology · Physiology · Polymerase chain reaction · Time · Transgenic mouse · Alleles · Animals · Cholesterol · DNA-Binding Proteins · Genotype · Hyperlipidemias · Leucine-Responsive Regulatory Protein · Lipid Metabolism · Lipoproteins · Mice · Mice, Transgenic · Polymerase Chain Reaction · Receptors, LDL · Time Factors · Transcription Factors · Triglycerides

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 highfat 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. Copyright © 2005 by the American Society for Biochemistry and Molecular Biology, Inc. Chemicals / CAS: lipid, 66455-18-3; triacylglycerol lipase, 9001-62-1; cholesterol, 57-88-5; Cholesterol, 57-88-5; DNA-Binding Proteins; Leucine-Responsive Regulatory Protein, 138791-20-5; Lipoproteins; Receptors, LDL; Transcription Factors; Triglycerides; VLDL receptor