title: High-fructose diet during periadolescent development increases depressive-like behavior and remodels the hypothalamic transcriptome in male rats.
abstract: Fructose consumption, which promotes insulin resistance, hypertension, and dyslipidemia, has increased by over 25% since the 1970s. In addition to metabolic dysregulation, fructose ingestion stimulates the hypothalamic-pituitary-adrenal (HPA) axis leading to elevations in glucocorticoids. Adolescents are the greatest consumers of fructose, and adolescence is a critical period for maturation of the HPA axis. Repeated consumption of high levels of fructose during adolescence has the potential to promote long-term dysregulation of the stress response. Therefore, we determined the extent to which consumption of a diet high in fructose affected behavior, serum corticosterone, and hypothalamic gene expression using a whole-transcriptomics approach. In addition, we examined the potential of a high-fructose diet to interact with exposure to chronic adolescent stress. Male Wistar rats fed the periadolescent high-fructose diet showed increased anxiety-like behavior in the elevated plus maze and depressive-like behavior in the forced swim test in adulthood, irrespective of stress history. Periadolescent fructose-fed rats also exhibited elevated basal corticosterone concentrations relative to their chow-fed peers. These behavioral and hormonal responses to the high-fructose diet did not occur in rats fed fructose during adulthood only. Finally, rats fed the high-fructose diet throughout development underwent marked hypothalamic transcript expression remodeling, with 966 genes (5.6%) significantly altered and a pronounced enrichment of significantly altered transcripts in several pathways relating to regulation of the HPA axis. Collectively, the data presented herein indicate that diet, specifically one high in fructose, has the potential to alter behavior, HPA axis function, and the hypothalamic transcriptome in male rats.
authors.affiliation: Department of Physiology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Constance S
authors.initials: CS
authors.lastname: Harrell
authors.affiliation: Neuroscience and Behavioral Biology Program, Emory University, Atlanta, GA 30322, USA.
authors.forename: Jillybeth
authors.initials: J
authors.lastname: Burgado
authors.affiliation: Department of Physiology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Kelly
authors.affiliation: Division of Developmental & Cognitive Neuroscience, Yerkes National Primate Research Center, USA.
authors.forename: Zachary P
authors.initials: ZP
authors.lastname: Johnson
authors.affiliation: Department of Physiology, Emory University, Atlanta, GA 30322, USA; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322, USA. Electronic address: gretchen.neigh@emory.edu.
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: Neigh
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003863:Depression / Q000378:metabolism* / Q000503:physiopathology; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D005632:Fructose / Q000008:administration & dosage*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000502:physiology; D059467:Transcriptome
chemical_list: D004040:Dietary Carbohydrates; D005632:Fructose
keywords: Adolescence; Depressive-like behavior; Diet; HPA axis; High-fructose; Stress