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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M700254-JLR200 on February 5, 2008

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Journal of Lipid Research, Vol. 49, 954-960, May 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

The LXR agonist T0901317 promotes the reverse cholesterol transport from macrophages by increasing plasma efflux potential

Ilaria Zanotti*, Francesco Potì*, Matteo Pedrelli*, Elda Favari*, Elsa Moleri{dagger}, Guido Franceschini{dagger}, Laura Calabresi{dagger} and Franco Bernini1,*

* Department of Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, 43100 Parma, Italy
{dagger} Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy

Published, JLR Papers in Press, February 5, 2008.

1 To whom correspondence should be addressed. e-mail: fbernini{at}unipr.it

The liver X receptors (LXRs) have been shown to affect lipoprotein plasma profile, lipid metabolism, and reverse cholesterol transport (RCT). In the present study, we investigated whether a short-term administration of the synthetic LXR agonist T0901317 (T0) to mice may affect RCT by modulating the capacity of plasma to promote cellular lipid efflux. Consistent with previous data, the pharmacological treatment of mice caused a significant increase of macrophage-derived [3H]cholesterol content in plasma, liver, and feces and resulted in improved capacity of plasma to promote cellular cholesterol release through passive diffusion and scavenger receptor class B type I (SR-BI)-mediated mechanisms. Differently, plasma from treated mice possessed similar or reduced capacity to drive lipid efflux via ABCA1. Consistent with these data, the analysis of plasma HDL fractions revealed that T0 caused the formation of larger, lipid-enriched particles. These results suggest that T0 promotes in vivo RCT from macrophages at least in part by inducing an enrichment of those HDL subclasses that increase plasma capacity to promote cholesterol efflux by passive diffusion and SR-BI-mediated mechanisms.

Supplementary key words liver X receptor • high density lipoprotein • passive diffusion • ATP binding cassette A1 • scavenger receptor class B type I

Abbreviations: cpt-cAMP, 8-(4-chlorophenylthio) cyclic AMP; LXR, liver X receptor; RCT, reverse cholesterol transport; SR-BI, scavenger receptor class B type I; SREBP-1, sterol-regulatory element binding protein-1; T0, T0901317


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