Each year in the United States, 38 million people suffer from acute gastroenteritis caused by unidentified agents. Deoxynivalenol is a mycotoxin elaborated from Fusarium species that might be a contributing agent to the large number of cases with unknown etiology. In humans, symptoms of acute DON intoxication include vomiting, diarrhea and abdominal pain, but lack of biomarker of effect for DON in humans has made evaluating the chronic adverse physiological consequences of DON impossible. Consequently, experimental animals have been utilized to predict DON's chronic effects in humans. In experimental animals, constant low-level DON exposure results in anorexia, weight suppression and growth hormone dysregulation, of which weight suppression serves as the foundation for the tolerable daily intake established by the Joint FAO/WHO Expert Committee on Food Additives. A primary mechanism by which DON causes weight suppression is through anorexia, yet the mechanisms of DON-induced anorexia are not well established. This impedes 1) comprehensive risk assessment of this mycotoxin, 2) potential mitigation efforts for weight suppression and 3) identification of particularly sensitive populations to DON's adverse physiological effects. Using a characterized mouse model, this dissertation addresses potential mechanisms of DON-induced anorexia with the overall hypothesis that DON-induced anorexia results from the peripheral release of gut satiety hormones that work in conjunction with the central nervous system (CNS) to reduce food intake. Results suggested anorexia occurred in a rapid (30 min) and transient nature, a manner that was consistent with both peripheral and central mechanisms. Notably, DON administration increased plasma satiety hormones peptide YY (PYY) and cholecystokinin (CCK) as early as 15 min post exposure, with peripheral PYY contributing modestly to DON's anorectic effects. In support of central action, DON was dose-dependently detected in the brain and hypothalamus beginning at 15 min. Intracerebroventricular injection (ICV) of DON resulted in decreased food intake, an effect previously reported by other researchers. Since PYY can act peripherally via the vagus nerve and centrally via central NPY2 receptors to reduce food intake, two additional studies were performed to confirm PYY's role in DON's anorectic effects. Results demonstrated that a subdiaphragmatic vagotomy could not attenuate anorexia induced by peripheral administered DON nor could centrally administered BIIE0246, a NPY2 receptor antagonist. Taken together, these results suggested the importance of peripheral PYY in DON-induced anorexia might be mediated by a mechanism other than the vagus nerve but that this mechanism was not linked to activation of central Y2 receptors.
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