title: Impact of aflatoxin B1 on hypothalamic neuropeptides regulating feeding behavior.
abstract: The presence of mycotoxins in food is a major problem of public health as they produce immunosuppressive, hepatotoxic and neurotoxic effects. Mycotoxins also induce mutagenic and carcinogenic effects after long exposure. Among mycotoxins that contaminate food are aflatoxins (AF) such as AFB1, which is the most powerful natural carcinogen. The AF poisoning results in symptoms of depression, anorexia, diarrhea, jaundice or anemia that can lead to death, but very few studies have explored the impact of AF on neuroendocrine regulations. To better understand the neurotoxic effects of AF related to anorexia, we explored in rat the impact of AFB1 on the major hypothalamic neuropeptides regulating feeding behavior, either orexigenic (NPY, Orexin, AgRP, MCH) or anorexigenic (α-MSH, CART, TRH). We also studied the effect of AFB1 on a novel neuropeptide, the secretogranin II (SgII)-derived peptide EM66, which has recently been linked to the control of food intake. For this, adult male rats were orally treated twice a week for 5 weeks with a low dose (150 μg/kg) or a high dose (300 μg/kg) of AFB1 dissolved in corn oil. Repeated exposure to AFB1 resulted in reduced body weight gain, which was highly significant for the high dose of AF. Immunocytochemical and quantitative PCR experiments revealed a dose-related decrease in the expression of all the hypothalamic neuropeptides studied in response to AFB1. Such orexigenic and anorexigenic alterations may underlie appetite disorders as they are correlated to a dose-dependent decrease in body weight gain of treated rats as compared to controls. We also found a decrease in the number of EM66-containing neurons in the arcuate nucleus of AFB1-treated animals, which was associated with a lower expression of its precursor SgII. These findings show for the first time that repeated consumption of AFB1 disrupts the hypothalamic regulation of neuropeptides involved in feeding behavior, which may contribute to the lower body weight gain associated to AF exposure.
authors.affiliation: Laboratory of Neuroendocrinology & Nutritional and climatic Environment, University Sidi Mohamed Ben Abdellah, Faculty of Sciences DM, Fez, Morocco; INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, Institute for Research and Innovation in Biomedicine (IRIB), 76821 Mont-Saint-Aignan, France; Normandy University, Caen, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Trebak
authors.affiliation: Laboratory of Neuroendocrinology & Nutritional and climatic Environment, University Sidi Mohamed Ben Abdellah, Faculty of Sciences DM, Fez, Morocco.
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Alaoui
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, Institute for Research and Innovation in Biomedicine (IRIB), 76821 Mont-Saint-Aignan, France; Normandy University, Caen, France.
authors.forename: David
authors.initials: D
authors.lastname: Alexandre
authors.affiliation: Laboratory of Neuroendocrinology & Nutritional and climatic Environment, University Sidi Mohamed Ben Abdellah, Faculty of Sciences DM, Fez, Morocco.
authors.forename: Seloua
authors.initials: S
authors.lastname: El Ouezzani
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, Institute for Research and Innovation in Biomedicine (IRIB), 76821 Mont-Saint-Aignan, France; Normandy University, Caen, France. Electronic address: youssef.anouar@univ-rouen.fr.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Anouar
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, Institute for Research and Innovation in Biomedicine (IRIB), 76821 Mont-Saint-Aignan, France; Normandy University, Caen, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chartrel
authors.affiliation: Laboratory of Neuroendocrinology & Nutritional and climatic Environment, University Sidi Mohamed Ben Abdellah, Faculty of Sciences DM, Fez, Morocco.
authors.forename: Rabia
authors.initials: R
authors.lastname: Magoul
mesh_terms: D016604:Aflatoxin B1 / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011042:Poisons / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009479:Neuropeptides; D011042:Poisons; D012333:RNA, Messenger; D016604:Aflatoxin B1
keywords: Aflatoxin B1; EM66; Food intake; Hypothalamus; Neurotoxicity; Orexigenic/anorexigenic neuropeptides