glycogen and Gastric-Dilatation

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.

Topics: Animals; Appetite Regulation; CCAAT-Enhancer-Binding Protein-alpha; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Fatty Acids; Fatty Liver; Gastric Dilatation; Gene Expression Regulation, Enzymologic; Glycogen; Lipid Metabolism Disorders; Liver; Male; Mice; Mice, Inbred C3H; Mycotoxins; Oxidation-Reduction; Phosphoenolpyruvate Carboxykinase (GTP); Phosphorylation; Protein Processing, Post-Translational; RNA, Messenger; Specific Pathogen-Free Organisms

Topics: Adrenal Cortex; Gastric Dilatation; Glycogen; Glycogenolysis; Myocardium; Stomach

Topics: Cytochromes; Electron Transport Complex IV; Gastric Dilatation; Glycogen; Myocardium; Pyruvates; Stomach Diseases