High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice

Juliane Zemdegs 1, 2, 3 Gaël Quesseveur 1 David Jarriault 2 Luc Pénicaud 2 Xavier Fioramonti 2 Bruno P. Guiard 3, 1, *
* Auteur correspondant
1 UFR Pharmacie - Université Paris-Sud
2 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
3 CRCA - Centre de Recherches sur la Cognition Animale
Abstract : 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.
Keywords : induced obesity arrive guidelines major depressive disorder serotonin reuptake inhibitors in-vivo microdialysis hippocampal neurogenesis indoleamine 2 3-dioxygenase insulin-resistance treatment response diabetes-mellitus
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01396978
Contributeur : Csga - Université de Bourgogne <>
Soumis le : mardi 15 novembre 2016 - 11:50:06
Dernière modification le : jeudi 20 février 2020 - 19:22:14

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UNIV-BOURGOGNE | CNRS | INRA | CRCA | CSGA | UNIV-PARIS-SACLAY | UNIV-TLSE2 | UNIV-TLSE3

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Juliane Zemdegs, Gaël Quesseveur, David Jarriault, Luc Pénicaud, Xavier Fioramonti, et al.. High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice. British Journal of Pharmacology, Wiley, 2016, 173 (13), pp.2095 - 2110. ⟨10.1111/bph.13343⟩. ⟨hal-01396978⟩

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