Anorectic response to the trichothecene T-2 toxin correspond to plasma elevations of the satiety hormone glucose-dependent insulinotropic polypeptide and peptide YY3-36

Abstract

T-2 toxin, a potent type A trichothecene mycotoxin, is produced by various Fusarium species and can negatively impact animal and human health. Although anorexia induction is a common hallmark of T-2 toxin-induced toxicity, the underlying mechanisms for this adverse effect are not fully understood. The goal of this study was to determine the roles of two gut satiety hormones, glucose-dependent insulinotropic polypeptide (GIP) and Peptide YY_3-36 (PYY_3-36) in anorexia induction by T-2 toxin. Elevations of plasma GIP and PYY_3-36 markedly corresponded to anorexia induction following oral exposure to T-2 toxin using a nocturnal mouse anorexia model. Direct administration of exogenous GIP and PYY_3-36 similarly induced anorectic responses. Furthermore, the GIP receptor antagonist Pro3GIP dose-dependently attenuated both GIP- and T-2 toxin-induced anorectic responses. Pretreatment with NPY2 receptor antagonist JNJ-31020028 induced a dose-dependent attenuation of both PYY_3-36- and T-2 toxin-induced anorectic responses. To summarize, these findings suggest that both GIP and PYY_3-36 might be critical mediators of anorexia induction by T-2 toxin.

Keywords: Anorexia; Glucose-dependent insulinotropic polypeptide; Mycotoxin; Peptide YY(3-36); T-2 toxin.