title: Deoxynivalenol-induced weight loss in the diet-induced obese mouse is reversible and PKR-independent.
abstract: The trichothecene deoxynivalenol (DON), a potent ribotoxic mycotoxin produced by the cereal blight fungus Fusarium graminearum, commonly contaminates grain-based foods. Oral exposure to DON causes decreased food intake, reduced weight gain and body weight loss in experimental animals - effects that have been linked to dysregulation of hormones responsible for mediating satiety at the central nervous system level. When diet-induced obese (DIO) mice are fed DON, they consume less food, eventually achieving body weights of control diet-fed mice. Here, we extended these findings by characterizing: (1) reversibility of DON-induced body weight loss and anorexia in DIO mice and (2) the role of double-stranded RNA-activated protein kinase (PKR) which has been previously linked to initiation of the ribotoxic stress response. The results demonstrated that DON-induced weight loss was reversible in DIO mice and this effect corresponded to initiation of a robust hyperphagic response. When DIO mice deficient in PKR were exposed to DON, they exhibited weight suppression similar to DIO wild-type fed the toxin, suggesting the toxin's weight effects were not dependent on PKR. Taken together, DON's effects on food consumption and body weight are not permanent and, furthermore, PKR is not an essential signaling molecule for DON's anorectic and weight effects.
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224, USA.
authors.forename: Brenna M
authors.initials: BM
authors.lastname: Flannery
authors.forename: Kaiyu
authors.initials: K
authors.lastname: He
authors.forename: James J
authors.initials: JJ
authors.lastname: Pestka
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005260:Female; D006963:Hyperphagia / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D012330:RNA, Double-Stranded; D020127:Recovery of Function; D012075:Remission, Spontaneous; D014255:Trichothecenes / Q000633:toxicity*; D015431:Weight Loss / Q000187:drug effects*; D028761:Withholding Treatment; D019892:eIF-2 Kinase / Q000172:deficiency / Q000378:metabolism*
chemical_list: D012330:RNA, Double-Stranded; D014255:Trichothecenes; D019892:eIF-2 Kinase; C007262:deoxynivalenol
keywords: ANOVA; Analysis of Variance; Anorexia; CCK; DIO; DON; Deoxynivalenol; IL-1β; IL-6; LFD; Mycotoxin; Obesity; PCR; PKR; PKR-KO; PKR-knockout; PYY; RNA-activated protein kinase; RSR; SOCS3; TNF-α; WT; Weight loss; cholecystokin; deoxynivalenol; diet-induced obese; interleukin-1β; interleukin-6; low fat diet; peptide YY; polymerase chain reaction; ribotoxic stress response; suppressor of cytokine signaling 3; tumor necrosis factor-α; wild type