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Journal Articles Archives of Toxicology Year : 2019

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

Marion Régnier
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Arnaud Polizzi
Céline Lukowicz
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Frédéric Lasserre
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Yannick Lippi
Claire Naylies
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Joëlle Laffitte
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Colette Bétoulières
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Alexandra Montagner
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Simon Ducheix
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Pascal Gourbeyre
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Sandrine Ellero-Simatos
Sandrine Ménard
Hervé Guillou
Isabelle P. Oswald
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Nicolas Loiseau
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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.
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hal-02619117 , version 1 (01-06-2023)



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⟩
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