High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice
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BACKGROUND AND PURPOSE: The link between type 2 diabetes mellitus (T2DM) and depression is bidirectional. However, the possibility that metabolic disorders may elicit anxiogenic-like/depressive-like symptoms or alter the efficacy of antidepressant drugs remains poorly documented. This study explored the influence of T2DM on emotionality and proposed a therapeutic strategy that might be used in depressed diabetic patients. EXPERIMENTAL APPROACH: Mice were fed a high-fat diet (HFD) and subjected to a full comprehensive metabolic and behavioural analysis to establish correlations between metabolic and psychiatric disorders. In vivo intra-hippocampal microdialysis was also applied to propose a mechanism underpinning the phenotype of mice fed the HFD. Finally, we tested whether chronic administration of the selective 5-HT reuptake inhibitor escitalopram or HFD withdrawal could reverse HFD-induced metabolic and behavioural anomalies. KEY RESULTS: The increased body weight, hyperglycaemia and impaired glucose tolerance in response to HFD were correlated with anxiogenic-like/depressive-like symptoms. Moreover, this phenotype was associated with decreased extracellular 5-HT levels in the hippocampus which may result from increased sensitivity of the dorsal raphe 5-HT1A autoreceptor. Interestingly, the beneficial effect of prolonged administration of escitalopram was abolished in HFD-fed mice. On the contrary, HFD withdrawal completely reversed metabolic impairments and positively changed symptoms of anxiety, although some behavioural anomalies persisted. CONCLUSIONS AND IMPLICATIONS: Our data provide clear-cut evidence that both pathologies are finely correlated and associated with impaired 5-HT mediated neurotransmission in the hippocampus. Further experiments are warranted to define the most adequate strategy for the treatment of such co-morbidity. LINKED ARTICLES: This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.
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Chronic HFD in male mice, leading to increased anxiety-like behavior, impairs basal electrical activity and excitability of serotonin neurons and serotonin-mediated neurotransmission in the hippocampus.
“Chronic HFD in male mice, leading to increased anxiety-like behavior, has been shown to impair the basal electrical activity and excitability of serotonin neurons as well as serotonin-mediated neurotransmission in the hippocampus [33,35].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [33]
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“Chronic HFD in male mice, leading to increased anxiety-like behavior, has been shown to impair the basal electrical activity and excitability of serotonin neurons as well as serotonin-mediated neurotransmission in the hippocampus [33,35].”
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- Authors
- Zemdegs, J., Quesseveur, G., Jarriault, D., Pénicaud, L., Fioramonti, X., & Guiard, B. P.
- Affiliations
- Université Paris-Sud (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Guiard, Bruno P.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2015-12-09
- Volume
- 173
- Issue
- 13
- Pages
- 2095-2110
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC4908198
- OpenAlex
- W1822601256
- Cited by
- 180
- References
- 80
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 20 · 2023: 18 · 2022: 16 · 2021: 31 · 2020: 22 · 2019: 14 · 2018: 13 · 2017: 7 · 2016: 12
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Société Française du Diabète
- National Council for Scientific and Technological Development (CNPq)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- high-fat diet, type 2 diabetes, depression, anxiety-like behavior, serotonin, 5-HT1A autoreceptors, hippocampus, escitalopram, glucose tolerance, hyperglycemia, monoaminergic systems, antidepressant efficacy
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Male, Metabolic Diseases, Mice, Inbred C57BL, Serotonin, Citalopram, Mice, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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