Cited by 166Gut microbiota and healthRegulation of Appetite and ObesityTryptophan and brain disorders

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High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome

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Hassan, Ahmed M., Mancano, Giulia, Kashofer, Karl, Fröhlich, Esther E., Matak, Andrija, Mayerhofer, Raphaela, Reichmann, Florian, Olivares, Marta, Neyrinck, Audrey M., Delzenne, Nathalie M., Claus, Sandrine P., Holzer, Peter·2019·Nutritional Neuroscience

DOI 10.1080/1028415x.2018.1465713

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Abstract

Objectives: The biological mechanisms linking diet-related obesity and depression remain unclear. Therefore, we examined the impact of high-fat diet (HFD) on murine behaviour, intestinal microbiome, brain metabolome, neuropeptide Y (NPY) expression, and dipeptidyl peptidase-4 (DPP-4) activity.Methods: Male C57Bl/6J mice were fed an HFD (60 kJ% from fat) or control diet (12 kJ% from fat) for 8 weeks, followed by behavioural phenotyping. Caecal microbiome was analysed by 16S rDNA sequencing, brain metabolome by 1H nuclear magnetic resonance, NPY expression by PCR and immunoassay, and dipeptidyl peptidase-4 (DPP-4) activity by enzymatic assay. The effect of a 4-week treatment with imipramine (7 mg/kg/day) and the DPP-4 inhibitor sitagliptin (50 mg/kg/day) on HFD-induced behavioural changes was also tested.Results: HFD led to a depression-like phenotype as revealed by reduced sociability and sucrose preference. In the caecum, HFD diminished the relative abundance of Bacteroidetes and increased the relative abundance of Firmicutes and Cyanobacteria. In the brain, HFD modified the metabolome of prefrontal cortex and striatum, changing the relative concentrations of molecules involved in energy metabolism (e.g. lactate) and neuronal signalling (e.g. γ-aminobutyric acid). The expression of NPY in hypothalamus and hippocampus was decreased by HFD, whereas plasma NPY and DPP-4-like activity were increased. The HFD-induced anhedonia remained unaltered by imipramine and sitagliptin.Discussion: The depression-like behaviour induced by prolonged HFD in mice is associated with distinct alterations of intestinal microbiome, brain metabolome, NPY system, and DPP-4-like activity. Importantly, the HFD-evoked behavioural disturbance remains unaltered by DPP-4 inhibition and antidepressant treatment with imipramine.

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Authors: Hassan, A. M., Mancano, G., Kashofer, K., Fröhlich, E. E., Matak, A., Mayerhofer, R., Reichmann, F., Olivares, M., Neyrinck, A. M., Delzenne, N. M., Claus, S. P., & Holzer, P.
Affiliations: Medical University of Graz (AT)
University of Reading (GB)
University of Graz (AT)
UCLouvain (BE)
Corresponding author: Holzer, Peter
ORCID: Hassan, Ahmed M.
Mancano, Giulia
Kashofer, Karl
Fröhlich, Esther E.
Mayerhofer, Raphaela
Reichmann, Florian
Olivares, Marta
Neyrinck, Audrey M.
Delzenne, Nathalie M.
Claus, Sandrine P.
Holzer, Peter
Venue: Nutritional Neuroscience
Publisher: Informa UK Limited
Published: 2018-04-26
Volume: 22
Issue: 12
Pages: 877-893
ISSN: 1028-415X (ISSN-L)
1476-8305
DOI: 10.1080/1028415x.2018.1465713
OpenAlex: W2800089222
Cited by: 166
References: 62
Citations by year: 2026: 9 · 2025: 16 · 2024: 22 · 2023: 17 · 2022: 26 · 2021: 34 · 2020: 23 · 2019: 12 · 2018: 7
FWCI: 6.77
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Nutritional Neuroscience (publishedVersion, cc-by)
PubMed (publishedVersion)
Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
Funders: EU (613979)
Austrian Science Fund
FWF (P25912-B23, W1241-B18)
European Commission
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: high-fat diet, depression-like behavior, obesity, gut microbiota, neuropeptide Y, dipeptidyl peptidase IV, brain metabolome, anhedonia, sociability, sucrose preference, imipramine, sitagliptin, prefrontal cortex, striatum, Bacteroidetes, Firmicutes, GABA, energy metabolism
MeSH terms: Gastrointestinal Microbiome, Animals, Behavior, Animal, Brain, Corpus Striatum, Depression, Male, Mice, Inbred C57BL, Neuropeptide Y, Weight Gain, Gene Expression, Prefrontal Cortex, Mice, Metabolome, Diet, High-Fat

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High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome

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