title: High vitamin A intake during pregnancy modifies dopaminergic reward system and decreases preference for sucrose in Wistar rat offspring.
abstract: High multivitamin (HV) content in gestational diets has long-term metabolic effects in rat offspring. These changes are associated with in utero modifications of gene expression in hypothalamic food intake regulation. However, the role of fat-soluble vitamins in mediating these effects has not been explored. Vitamin A is a plausible candidate due to its role in gene methylation. Vitamin A intake above requirements during pregnancy affects the development of neurocircuitries involved in food intake and reward regulation. Pregnant Wistar rats were fed AIN-93G diets with the following content: recommended multivitamins (1-fold multivitamins: RV), high vitamin A (10-fold vitamin A: HA) or HV with only recommended vitamin A (10-fold multivitamins, 1-fold vitamin A: HVRA). Body weight, food intake and preference, mRNA expression and DNA methylation of hippocampal dopamine-related genes were assessed in male offspring brains at different developmental windows: birth, weaning and 14weeks postweaning. HA offspring had changes in dopamine-related gene expression at all developmental windows and DNA hypermethylation in the dopamine receptor 2 promoter region compared to RV offspring. Furthermore, HA diet lowered sucrose preference but had no effect on body weight and expression of hypothalamic genes. In contrast, HVRA offspring showed only at adulthood changes in expression of hippocampal genes and a modest effect on hypothalamic genes. High vitamin A intake alone in gestational diets has long-lasting programming effects on the dopaminergic system that are further translated into decreased sucrose preference but not food intake.
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: diana.sanchezhernandez@mail.utoronto.ca.
authors.forename: Diana
authors.initials: D
authors.lastname: Sánchez-Hernández
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: abepoon87@gmail.com.
authors.forename: Abraham N
authors.initials: AN
authors.lastname: Poon
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: ruslan.kubant@gmail.com.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Kubant
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: brianhk.kim@mail.utoronto.ca.
authors.forename: Hwanki
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: pedro.huot@mail.utoronto.ca.
authors.forename: Pedro S P
authors.initials: PS
authors.lastname: Huot
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: cec297@cornell.edu.
authors.forename: Clara E
authors.initials: CE
authors.lastname: Cho
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: e.pannia@mail.utoronto.ca.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pannia
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: sandyreza01@yahoo.com.mx.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Reza-López
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2; Hospital for Sick Children, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: zdenka.pausova@sickkids.ca.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: richard.bazinet@utoronto.ca.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2; Department of Physiology, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Electronic address: harvey.anderson@utoronto.ca.
authors.forename: G Harvey
authors.initials: GH
authors.lastname: Anderson
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D013395:Sucrose / Q000008:administration & dosage*; D014801:Vitamin A / Q000008:administration & dosage*
chemical_list: D014801:Vitamin A; D013395:Sucrose; D004298:Dopamine
keywords: Dopamine; Epigenetics; Gestation; Hippocampus; Reward system; Vitamin A