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Papers In Press, published online ahead of print March 16, 2005
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Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, Zuid-Holland 2300 RC
Corresponding Author: P.C.N.Rensen{at}lumc.nl
The VLDL receptor (VLDLR), LDL receptor (LDLR), and LRP are the three main apoE-recognizing endocytic receptors involved in the clearance of triglyceride (TG)-rich lipoproteins from plasma. Whereas LDLR-deficiency in mice results in accumulation of plasma LDL-sized lipoproteins, VLDLR or LRP deficiency alone only minimally affect plasma lipoproteins. To investigate the combined effect of the absence of these receptors on TG-rich lipoprotein levels, we now generated unique VLDLR, LDLR, and LRP triple-deficient mice. As compared with wild-type mice, these mice markedly accumulated plasma lipids and lipases. These mice did not show aggravated hyperlipidemia as compared with LDLR and LRP double-deficient mice, but plasma TG was elevated after high-fat diet feeding. In addition, these mice showed a severely decreased postprandial TG clearance typical of VLDLR-deficient mice. Collectively, although VLDLR-deficiency in LRP and LDLR-deficient mice does not aggravate hyperlipidemia, these triple-deficient mice represent a unique model of markedly delayed TG clearance on a hyperlipidemic background.
Revised on March 16, 2005
Accepted on March 9, 2005
Triglyceride-rich lipoprotein metabolism in unique VLDL receptor, LDL receptor, and LRP triple-deficient mice
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