Rexinoid bexarotene modulates triglyceride but not cholesterol metabolism via gene-specific permissivity of the RXR/LXR heterodimer in the liver.

Abstract : OBJECTIVE: Bexarotene (Targretin) is a clinically used antitumoral agent which exerts its action through binding to and activation of the retinoid-X-receptor (RXR). The most frequent side-effect of bexarotene administration is an increase in plasma triglycerides, an independent risk factor of cardiovascular disease. The molecular mechanism behind this hypertriglyceridemia remains poorly understood. METHODS AND RESULTS: Using wild-type and LXR alpha/beta-deficient mice, we show here that bexarotene induces hypertriglyceridemia and activates hepatic LXR-target genes of lipogenesis in an LXR-dependent manner, hence exerting a permissive effect on RXR/LXR heterodimers. Interestingly, RNA analysis and Chromatin Immunoprecipitation assays performed in the liver reveal that the in vivo permissive effect of bexarotene on the RXR/LXR heterodimer is restricted to lipogenic genes without modulation of genes controlling cholesterol homeostasis. CONCLUSIONS: These findings demonstrate that the hypertriglyceridemic action of bexarotene occurs via the RXR/LXR heterodimer and show that RXR heterodimers can act with a selective permissivity on target genes of specific metabolic pathways in the liver.
Type de document :
Article dans une revue
Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2009, 29 (10), pp.1488-95. 〈10.1161/ATVBAHA.109.189506〉
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00410108
Contributeur : Marie-Hélène Derudas <>
Soumis le : vendredi 8 janvier 2010 - 11:40:24
Dernière modification le : jeudi 26 avril 2018 - 01:04:36
Document(s) archivé(s) le : mardi 18 septembre 2012 - 12:56:34

Fichiers

inserm-00410108_edited.pdf
Fichiers produits par l'(les) auteur(s)


Identifiants

Collections

Citation

Fanny Lalloyer, Thomas Åskov Pedersen, Barbara Gross, Sophie Lestavel, Saïd Yous, et al.. Rexinoid bexarotene modulates triglyceride but not cholesterol metabolism via gene-specific permissivity of the RXR/LXR heterodimer in the liver.. Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2009, 29 (10), pp.1488-95. 〈10.1161/ATVBAHA.109.189506〉. 〈inserm-00410108〉

Partager

Métriques

Consultations de la notice

280

Téléchargements de fichiers

636