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Cited by 107Stress Responses and CortisolDiet, Metabolism, and DiseaseRegulation of Appetite and Obesity

High-fructose diet during periadolescent development increases depressive-like behavior and remodels the hypothalamic transcriptome in male rats

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Harrell, Constance S., Burgado, Jillybeth, Kelly, Sean D., Johnson, Zachary P., Neigh, Gretchen N.·2015·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2015.08.025PMC PMC4637272
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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.

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  • In male Wistar rats, a high fructose diet might alter behaviour, hypothalamic-pituitary-adrenal axis function, and the hypothalamic transcriptome, inducing anxiety-like behaviour and depressive-like behaviour.

    “Data from an animal study showed that a high fructose diet might alter behaviour, hypothalamic-pituitary-adrenal axis function, and the hypothalamic transcriptome in male Wistar rats, inducing anxiety-like behaviour and depressive-like behaviour.125”

    From Dietary sugar consumption and health: umbrella review (2023) · cites this paper as [125]

  • Prolonged intake of high sucrose or fructose diets can induce anxiety- and depressive-like behaviors and motivational deficits in rodents.

    “While sugar consumption can alleviate stress and pain and improve negative mood and emotional states in the short-term [52], prolonged intake of high sucrose or fructose diets can induce anxiety-and depressive-like behaviors and motivational deficits [53][54][55], effects that are more pronounced during the adolescent period [55][56][57].”

    From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [55]

  • The effects of prolonged high sugar intake on anxiety- and depressive-like behaviors are more pronounced during the adolescent period.

    “While sugar consumption can alleviate stress and pain and improve negative mood and emotional states in the short-term [52], prolonged intake of high sucrose or fructose diets can induce anxiety-and depressive-like behaviors and motivational deficits [53][54][55], effects that are more pronounced during the adolescent period [55][56][57].”

    From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [55]

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Research works printed but not linked: 1

  1. McCormick CM Thomas CM Sheridan CS Nixon F Flynn JA Mathews IZ Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood Hippocampus 2012 22 1300 1312 21805526

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Authors
Harrell, C. S., Burgado, J., Kelly, S. D., Johnson, Z. P., & Neigh, G. N.
Affiliations
  • Emory University (US)
  • Emory National Primate Research Center (US)
Corresponding author
Neigh, Gretchen N.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2015-12
Volume
62
Pages
252-264
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2015.08.025
PMC
PMC4637272
OpenAlex
W2147527484
Cited by
107
References
74
Citations by year
2026: 8 · 2025: 10 · 2024: 14 · 2023: 17 · 2022: 15 · 2021: 16 · 2020: 6 · 2019: 10 · 2018: 7 · 2017: 1 · 2016: 3
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (R21MH091321)
  • National Institute of General Medical Sciences (T32GM008169)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
high-fructose diet, fructose consumption, depression-like behavior, anxiety-like behavior, hypothalamic-pituitary-adrenal axis, corticosterone, insulin resistance, glucocorticoids, stress response
MeSH terms
Animals, Behavior, Animal, Depression, Dietary Carbohydrates, Fructose, Hypothalamo-Hypophyseal System, Hypothalamus, Male, Pituitary-Adrenal System, Sexual Maturation, Rats, Wistar, Rats, Transcriptome

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