The protective role of liver X receptor (LXR) during fumonisin B1-induced hepatotoxicity - Génétique, reproduction et développement Accéder directement au contenu
Article Dans Une Revue Archives of Toxicology Année : 2019

The protective role of liver X receptor (LXR) during fumonisin B1-induced hepatotoxicity

Marion Régnier
  • Fonction : Auteur
  • PersonId : 1073447
Arnaud Polizzi
Céline Lukowicz
  • Fonction : Auteur
  • PersonId : 1017606
Frédéric Lasserre
  • Fonction : Auteur
  • PersonId : 1202853
Yannick Lippi
Claire Naylies
  • Fonction : Auteur
  • PersonId : 1041410
Joëlle Laffitte
  • Fonction : Auteur
Colette Bétoulières
  • Fonction : Auteur
Alexandra Montagner
  • Fonction : Auteur
Simon Ducheix
  • Fonction : Auteur
Pascal Gourbeyre
  • Fonction : Auteur
Sandrine Ellero-Simatos
Sandrine Ménard
Hervé Guillou
Isabelle P. Oswald
Connectez-vous pour contacter l'auteur
Nicolas Loiseau
Connectez-vous pour contacter l'auteur

Résumé

Fumonisin B1 (FB1), a congener of fumonisins produced by Fusarium species, is the most abundant and most toxicologically active fumonisin. FB1 causes severe mycotoxicosis in animals, including nephrotoxicity, hepatotoxicity, and disruption of the intestinal barrier. However, mechanisms associated with FB1 toxicity are still unclear. Preliminary studies have highlighted the role of liver X receptors (LXRs) during FB1 exposure. LXRs belong to the nuclear receptor family and control the expression of genes involved in cholesterol and lipid homeostasis. In this context, the toxicity of FB1 was compared in female wild-type (LXR+/+) and LXR, double knockout (LXR-/-) mice in the absence or presence of FB1 (10mg/kg body weight/day) for 28days. Exposure to FB1 supplemented in the mice's drinking water resulted in more pronounced hepatotoxicity in LXR-/- mice compared to LXR+/+ mice, as indicated by hepatic transaminase levels (ALT, AST) and hepatic inflammatory and fibrotic lesions. Next, the effect of FB1 exposure on the liver transcriptome was investigated. FB1 exposure led to a specific transcriptional response in LXR-/- mice that included altered cholesterol and bile acid homeostasis. ELISA showed that these effects were associated with an elevated FB1 concentration in the plasma of LXR-/- mice, suggesting that LXRs participate in intestinal absorption and/or clearance of the toxin. In summary, this study demonstrates an important role of LXRs in protecting the liver against FB1-induced toxicity, suggesting an alternative mechanism not related to the inhibition of sphingolipid synthesis for mycotoxin toxicity.
Fichier principal
Vignette du fichier
Regnier et al 2019.pdf (3.76 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-02619117 , version 1 (01-06-2023)

Identifiants

Citer

Marion Régnier, Arnaud Polizzi, Céline Lukowicz, Sarra Smati, Frédéric Lasserre, et al.. The protective role of liver X receptor (LXR) during fumonisin B1-induced hepatotoxicity. Archives of Toxicology, 2019, 93 (2), pp.505-517. ⟨10.1007/s00204-018-2345-2⟩. ⟨hal-02619117⟩
77 Consultations
24 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More