Triglyceride-rich lipoprotein metabolism in unique VLDL receptor, LDL receptor, and LRP triple-deficient mice.
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.
Espirito Santo
Sonia M S
SM
Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands.
Rensen
Patrick C N
PC
Goudriaan
Jeltje R
JR
Bensadoun
André
A
Bovenschen
Niels
N
Voshol
Peter J
PJ
Havekes
Louis M
LM
van Vlijmen
Bart J M
BJ
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
D004268:DNA-Binding Proteins; D008074:Lipoproteins; D011973:Receptors, LDL; D014157:Transcription Factors; D014280:Triglycerides; C036053:VLDL receptor; D051756:Leucine-Responsive Regulatory Protein; D002784:Cholesterol