title: High density lipoprotein metabolism in low density lipoprotein receptor-deficient mice.
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.
authors: Department of Medicine, University Hospital Hamburg Eppendorf, 20246 Hamburg, Germany.
authors: Franz
authors: F
authors: Rinninger
authors: Department of Biochemistry and Molecular Cell Biology, University Hospital Hamburg Eppendorf, 20246 Hamburg, Germany.
authors: Markus
authors: M
authors: Heine
authors: 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.
authors: Roshni
authors: R
authors: Singaraja
authors: Centre for Molecular Medicine and Therapeutics and Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors: Michael
authors: M
authors: Hayden
authors: Department of Medicine, University Hospital Hamburg Eppendorf, 20246 Hamburg, Germany.
authors: May
authors: M
authors: Brundert
authors: Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
authors: Rajasekhar
authors: R
authors: Ramakrishnan
authors: Department of Biochemistry and Molecular Cell Biology, University Hospital Hamburg Eppendorf, 20246 Hamburg, Germany.
authors: Joerg
authors: J
authors: Heeren
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D064286:ATP Binding Cassette Transporter 1; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D011973:Receptors, LDL; D014280:Triglycerides; C577833:Abca1 protein, mouse
keywords: cholesteryl ester; scavenger receptor class B type I; selective uptake