Rubratoxin B induces signs of fatty acid oxidation disorders (FAODs) in mice.

Abstract

Rubratoxin B is a mycotoxin that causes hypoglycemia and fatty liver. We investigated the effect of rubratoxin B on hepatic glycogen content and regulation, because blood glucose levels are associated with hepatic glycogen storage. Mice were treated with 1.5mg/kg rubratoxin B for 24h. Stomachs of treated mice became extremely swollen, and the contents were significantly heavier than those of controls. Hypoglycemia stimulates appetite; therefore, rubratoxin B may perturb satiation. Rubratoxin B evidently depleted hepatic glycogen stores. Phosphoenolpyruvate carboxykinase (PEPCK) activity and mRNA levels in treated mice were reduced, indicating that rubratoxin B caused hepatic glycogen depletion by inhibiting PEPCK. PEPCK activity and mRNA levels were reduced to similar degrees; it appears that PEPCK activity is regulated transcriptionally. Levels of the PEPCK gene trans-activators phospho-CREB (active form) and C/EBPα were significantly reduced in the livers of treated mice, suggesting that these factors are important for PEPCK gene transcription. Rubratoxicosis and fatty acid oxidation disorders (FAODs) share characteristic signs, such as robust appetite, hypoglycemia, hepatic glycogen depletion, and fatty liver. Although FAODs are generally considered genetic deficiencies, our results indicate that a chemical can also cause FAOD-like signs in mice.

• Authors: Keiko Iwashita, Hitoshi Nagashima
• Journal: Toxicology letters (Toxicol Lett) Vol. 206 Issue 2 Pg. 238-43 (Oct 10 2011) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 21835235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• CCAAT-Enhancer-Binding Protein-alpha
• Creb1 protein, mouse
• Cyclic AMP Response Element-Binding Protein
• Fatty Acids
• Mycotoxins
• RNA, Messenger
• rubratoxins
• Glycogen
• Phosphoenolpyruvate Carboxykinase (GTP)

Topics

• Animals
• Appetite Regulation (drug effects)
• CCAAT-Enhancer-Binding Protein-alpha (metabolism)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Disease Models, Animal
• Fatty Acids (metabolism)
• Fatty Liver (etiology)
• Gastric Dilatation (etiology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Glycogen (metabolism)
• Lipid Metabolism Disorders (chemically induced, metabolism, physiopathology)
• Liver (drug effects, enzymology, metabolism)
• Male
• Mice
• Mice, Inbred C3H
• Mycotoxins (toxicity)
• Oxidation-Reduction (drug effects)
• Phosphoenolpyruvate Carboxykinase (GTP) (genetics, metabolism)
• Phosphorylation (drug effects)
• Protein Processing, Post-Translational (drug effects)
• RNA, Messenger (metabolism)
• Specific Pathogen-Free Organisms