Title: PXR agonism decreases plasma HDL levels in ApoE3-Leiden.CETP mice
Authors: de Haan, Willeke ×
de Vries-van der Weij, Jitske
Mol, Isabel M
Hoekstra, Menno
Romijn, Johannes A
Jukema, J Wouter
Havekes, Louis M
Princen, Hans M G
Rensen, Patrick C N #
Issue Date: Mar-2009
Publisher: Elsevier Science
Series Title: Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids vol:1791 issue:3 pages:191-7
Article number: 10.1016/j.bbalip.2008.12.008
Abstract: Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE3-Leiden (E3L) and E3L.CETP mice, well-established models for human-like lipoprotein metabolism. Female mice were fed a diet with increasing amounts of the potent PXR agonist 5-pregnen-3beta-ol-20-one-16alpha-carbonitrile (PCN). In E3L and E3L.CETP mice, PCN increased liver lipids as well as plasma cholesterol and triglycerides. However, whereas PCN increased cholesterol contained in large HDL-1 particles in E3L mice, it dose-dependently decreased HDL-cholesterol in E3L.CETP mice, indicating that CETP expression dominates the effect of PCN on HDL metabolism. Analysis of the hepatic expression of genes involved in HDL metabolism showed that PCN decreased expression of genes involved in HDL synthesis (Abca1, Apoa1), maturation (Lcat, Pltp) and clearance (Sr-b1). The HDL-increasing effect of PCN, observed in E3L mice, is likely caused by a marked decrease in hepatic SR-BI protein expression, and completely reversed by CETP expression. We conclude that chronic PXR agonism dose-dependently reduces plasma HDL-cholesterol in the presence of CETP.
ISSN: 1388-1981
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science