title: Anorexic action of deoxynivalenol in hypothalamus and intestine.
abstract: Although deoxynivalenol (DON) suppresses food intake and subsequent weight gain, its contribution to anorexia mechanisms has not been fully clarified. Thus, we investigated the anorexic actions of DON in the hypothalamus and intestine, both organs related to appetite. When female B6C3F1 mice were orally exposed to different doses of DON, a drastic anorexic action was observed at a dose of 12.5 mg/kg body weight (bw) from 0 to 3 h after administration. Exposure to DON (12.5 mg/kg bw) for 3 h significantly increased the hypothalamic mRNA levels of anorexic pro-opiomelanocortin (POMC) and its downstream targets, including melanocortin 4 receptor, brain-derived neurotrophic factor, and tyrosine kinase receptor B; at the same time, orexigenic hormones were not affected. In addition, exposure to DON significantly elevated the hypothalamic mRNA levels of proinflammatory cytokines (IL-1β, TNF-α, and IL-6) and activated nuclear factor-kappa B (NF-κB), an upstream factor of POMC. These results suggest that DON-induced proinflammatory cytokines increased the POMC level via NF-κB activation. Moreover, exposure to DON significantly enhanced the gastrointestinal mRNA levels of anorexic cholecystokinin (CCK) and transient receptor potential ankyrin-1 channel (TRPA1), a possible target of DON; these findings suggest that DON induced anorexic action by increasing CCK production via TRPA1. Taken together, these results suggest that DON induces anorexic POMC, perhaps via NF-κB activation, by increasing proinflammatory cytokines in the hypothalamus and brings about CCK production, possibly through increasing intestinal TRPA1 expression, leading to anorexic actions.
authors.affiliation: Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Tominaga
authors.affiliation: Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Momonaka
authors.affiliation: Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yokose
authors.affiliation: Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tadaishi
authors.affiliation: Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamane
authors.affiliation: Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oishi
authors.affiliation: Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan. Electronic address: k2kobaya@nodai.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi-Hattori
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D001067:Appetite Depressants / Q000008:administration & dosage / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake / Q000187:drug effects; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000819:agonists / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D020813:Receptor, trkB / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D001067:Appetite Depressants; D019208:Brain-Derived Neurotrophic Factor; D004785:Environmental Pollutants; D018836:Inflammation Mediators; C574273:MC4R protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; D014255:Trichothecenes; D011333:Pro-Opiomelanocortin; D020813:Receptor, trkB; C007262:deoxynivalenol
keywords: Anorexia; Cholecystokinin; Deoxynivalenol; Hypothalamus; Inflammatory cytokines; Intestine