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

Journal of Lipid Research

Niels Bovenschen¹  Patrick C.N. Rensen¹  André Bensadoun²  Louis M. Havekes³  Peter J. Voshol⁴  Sonia M. S. Espirito Santo⁴  Bart J.M. van Vlijmen⁴  Jeltje R. Goudriaan⁵ 

[1] Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands;Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands;Division of Nutritional Sciences, Cornell University, Ithaca, NY;Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands;To whom correspondence should be addressed.;

关键词: apolipoprotein E;    hepatic lipase;    hyperlipidemia;    lipid metabolism;    lipoprotein lipase;    postprandial response;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown