Body composition and hormonal effects following exposure to mycotoxin deoxynivalenol in the high-fat diet-induced obese mouse

Scope: To characterize the effects of ingesting the common foodborne mycotoxin deoxynivalenol (DON) on body weight and composition in the high‐fat (HF) diet‐induced obese mice, a model of human obesity. Methods and results: Female B6C3F1 mice were initially fed HF diets containing 45% kcal (HF45) or 60% kcal (HF60) as fat for 94 days to induce obesity. Half of each group was either continued on unamended HF diets or fed HF diets containing 10 mg/kg DON (DON‐HF45 or DON‐HF60) for another 54 days. Additional control mice were fed a low‐fat (LF) diet containing 10% kcal as fat for the entire 148‐day period. DON induced rapid decreases in body weights and fat mass, which stabilized to those of the LF control within 11 days. These effects corresponded closely to a robust transient decrease in food consumption. While lean body mass did not decline in DON‐fed groups, further increases were suppressed. DON exposure reduced plasma insulin, leptin, insulin‐like growth factor 1, and insulin‐like growth factor acid labile subunit as well as increased hypothalamic mRNA level of the orexigenic agouti‐related protein. Conclusion: DON‐mediated effects on body weight, fat mass, food intake, and hormonal levels in obese mice were consistent with a state of chronic energy restriction.