The LXR agonist T0901317 promotes the reverse cholesterol transport from macrophages by increasing plasma efflux potential.
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.
Zanotti
Ilaria
I
Department of Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, 43100 Parma, Italy.
Potì
Francesco
F
Pedrelli
Matteo
M
Favari
Elda
E
Moleri
Elsa
E
Franceschini
Guido
G
Calabresi
Laura
L
Bernini
Franco
F
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D019556:COS Cells; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D000882:Haplorhini; D006845:Hydrocarbons, Fluorinated; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D057093:Orphan Nuclear Receptors; D016133:Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D008055:Lipids; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides