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J Lipid Res. 2014 Sep;55(9):1914-24. doi: 10.1194/jlr.M048819. Epub 2014 Jun 22.

High density lipoprotein metabolism in low density lipoprotein receptor-deficient mice.

Author information

1
Department of Medicine, University Hospital Hamburg Eppendorf, 20246 Hamburg, Germany.
2
Department of Biochemistry and Molecular Cell Biology, University Hospital Hamburg Eppendorf, 20246 Hamburg, Germany.
3
Translational Laboratories in Genetic Medicine, Agency for Science, Technology and Research National University of Singapore, Singapore 117609 Department of Medicine, National University of Singapore, Singapore 117609.
4
Centre for Molecular Medicine and Therapeutics and Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
5
Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY 10032.

Abstract

The LDL receptor (LDLR) and scavenger receptor class B type I (SR-BI) play physiological roles in LDL and HDL metabolism in vivo. In this study, we explored HDL metabolism in LDLR-deficient mice in comparison with WT littermates. Murine HDL was radiolabeled in the protein ((125)I) and in the cholesteryl ester (CE) moiety ([(3)H]). The metabolism of (125)I-/[(3)H]HDL was investigated in plasma and in tissues of mice and in murine hepatocytes. In WT mice, liver and adrenals selectively take up HDL-associated CE ([(3)H]). In contrast, in LDLR(-/-) mice, selective HDL CE uptake is significantly reduced in liver and adrenals. In hepatocytes isolated from LDLR(-/-) mice, selective HDL CE uptake is substantially diminished compared with WT liver cells. Hepatic and adrenal protein expression of lipoprotein receptors SR-BI, cluster of differentiation 36 (CD36), and LDL receptor-related protein 1 (LRP1) was analyzed by immunoblots. The respective protein levels were identical both in hepatic and adrenal membranes prepared from WT or from LDLR(-/-) mice. In summary, an LDLR deficiency substantially decreases selective HDL CE uptake by liver and adrenals. This decrease is independent from regulation of receptor proteins like SR-BI, CD36, and LRP1. Thus, LDLR expression has a substantial impact on both HDL and LDL metabolism in mice.

KEYWORDS:

cholesteryl ester; scavenger receptor class B type I; selective uptake

PMID:
24954421
PMCID:
PMC4617360
DOI:
10.1194/jlr.M048819
[Indexed for MEDLINE]
Free PMC Article

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