Anorexia induction by the trichothecene deoxynivalenol (vomitoxin) is mediated by the release of the gut satiety hormone peptide YY.

Abstract

Consumption of deoxynivalenol (DON), a trichothecene mycotoxin known to commonly contaminate grain-based foods, suppresses growth of experimental animals, thus raising concerns over its potential to adversely affect young children. Although this growth impairment is believed to result from anorexia, the initiating mechanisms for appetite suppression remain unknown. Here, we tested the hypothesis that DON induces the release of satiety hormones and that this response corresponds to the toxin's anorectic action. Acute ip exposure to DON had no effect on plasma glucagon-like peptide-1, leptin, amylin, pancreatic polypeptide, gastric inhibitory peptide, or ghrelin; however, the toxin was found to robustly elevate peptide YY (PYY) and cholecystokinin (CCK). Specifically, ip exposure to DON at 1 and 5mg/kg bw induced PYY by up to 2.5-fold and CCK by up to 4.1-fold. These responses peaked within 15-120 min and lasted up to 120 min (CCK) and 240 min (PPY), corresponding with depressed rates of food intake. Direct administration of exogenous PYY or CCK similarly caused reduced food intake. Food intake experiments using the NPY2 receptor antagonist BIIE0246 and the CCK1A receptor antagonist devazepide, individually, suggested that PYY mediated DON-induced anorexia but CCK did not. Orolingual exposure to DON induced plasma PYY and CCK elevation and anorexia comparable with that observed for ip exposure. Taken together, these findings suggest that PYY might be one critical mediator of DON-induced anorexia and, ultimately, growth suppression.

• Authors: Brenna M Flannery, Erica S Clark, James J Pestka
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 130 Issue 2 Pg. 289-97 (Dec 2012) ISSN: 1096-0929 [Electronic] United States
• PMID: 22903826 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Appetite Depressants
• Benzazepines
• Ccl28 protein, mouse
• Chemokines, CC
• Mycotoxins
• Receptors, Cholecystokinin
• Receptors, Neuropeptide Y
• Trichothecenes
• neuropeptide Y2 receptor
• Peptide YY
• Cholecystokinin
• Arginine
• Devazepide
• deoxynivalenol
• BIIE 0246

Topics

• Administration, Oral
• Animals
• Anorexia (blood, chemically induced, physiopathology, psychology)
• Appetite Depressants (administration & dosage, toxicity)
• Appetite Regulation (drug effects)
• Arginine (analogs & derivatives, pharmacology)
• Behavior, Animal (drug effects)
• Benzazepines (pharmacology)
• Chemokines, CC
• Cholecystokinin (blood)
• Devazepide (pharmacology)
• Dose-Response Relationship, Drug
• Eating (drug effects)
• Female
• Food Contamination
• Injections, Intraperitoneal
• Mice
• Mycotoxins (administration & dosage, toxicity)
• Peptide YY (blood)
• Receptors, Cholecystokinin (drug effects, metabolism)
• Receptors, Neuropeptide Y (drug effects, metabolism)
• Satiation
• Time Factors
• Trichothecenes (administration & dosage, toxicity)