HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M700108-JLR200v1 48/8/1763    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van der Hoogt, C. C. Articles by Rensen, P. C. N. Search for Related Content PubMed PubMed Citation Articles by van der Hoogt, C. C. Articles by Rensen, P. C. N. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 48, 1763-1771, August 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Fenofibrate increases HDL-cholesterol by reducing cholesteryl ester transfer protein expression

Caroline C. van der Hoogt^1,*,, Willeke de Haan^1,*,, Marit Westerterp^*,, Menno Hoekstra, Geesje M. Dallinga-Thie^**, Johannes A. Romijn, Hans M. G. Princen^*, J. Wouter Jukema, Louis M. Havekes^*,, and Patrick C. N. Rensen^2,*,

^* Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, 2301 CE Leiden, The Netherlands
Department of General Internal Medicine, Endocrinology, and Metabolic Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
Leiden/Amsterdam Center for Drug Research, Division of Biopharmaceutics, 2300 RA Leiden, The Netherlands
^** Department of Internal Medicine, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands

Published, JLR Papers in Press, May 24, 2007.

¹ C. C. van der Hoogt and W. de Haan contributed equally to this study.

² To whom correspondence should be addressed. e-mail: p.c.n.rensen{at}lumc.nl

In addition to efficiently decreasing VLDL-triglycerides (TGs), fenofibrate increases HDL-cholesterol levels in humans. We investigated whether the fenofibrate-induced increase in HDL-cholesterol is dependent on the expression of the cholesteryl ester transfer protein (CETP). To this end, APOE*3-Leiden (E3L) transgenic mice without and with the human CETP transgene, under the control of its natural regulatory flanking regions, were fed a Western-type diet with or without fenofibrate. Fenofibrate (0.04% in the diet) decreased plasma TG in E3L and E3L.CETP mice (–59% and –60%; P < 0.001), caused by a strong reduction in VLDL. Whereas fenofibrate did not affect HDL-cholesterol in E3L mice, fenofibrate dose-dependently increased HDL-cholesterol in E3L.CETP mice (up to +91%). Fenofibrate did not affect the turnover of HDL-cholesteryl ester (CE), indicating that fenofibrate causes a higher steady-state HDL-cholesterol level without altering the HDL-cholesterol flux through plasma. Analysis of the hepatic gene expression profile showed that fenofibrate did not differentially affect the main players in HDL metabolism in E3L.CETP mice compared with E3L mice. However, in E3L.CETP mice, fenofibrate reduced hepatic CETP mRNA (–72%; P < 0.01) as well as the CE transfer activity in plasma (–73%; P < 0.01). We conclude that fenofibrate increases HDL-cholesterol by reducing the CETP-dependent transfer of cholesterol from HDL to (V)LDL, as related to lower hepatic CETP expression and a reduced plasma (V)LDL pool.

Supplementary key words fibrate • high density lipoprotein • peroxisome proliferator-activated receptor • transgenic mice

Abbreviations: apoE, apolipoprotein E; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; COEth, cholesteryl oleyl ether; E3L, APOE*3-Leiden; FCR, fractional catabolic rate; LXR, liver X receptor; PLTP, phospholipid transfer protein; PPAR, peroxisome proliferator-activated receptor ; PPRE, peroxisome proliferator response element; SR-BI, scavenger receptor class B type I; TC, total plasma cholesterol; TG, triglyceride

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				W. de Haan, J. de Vries-van der Weij, J. W.A. van der Hoorn, T. Gautier, C. C. van der Hoogt, M. Westerterp, J. A. Romijn, J. W. Jukema, L. M. Havekes, H. M.G. Princen, et al. Torcetrapib Does Not Reduce Atherosclerosis Beyond Atorvastatin and Induces More Proinflammatory Lesions Than Atorvastatin Circulation, May 13, 2008; 117(19): 2515 - 2522. [Abstract] [Full Text] [PDF]