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

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.
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Contributor : Csga - Université de Bourgogne Connect in order to contact the contributor
Submitted on : Tuesday, November 15, 2016 - 11:50:06 AM
Last modification on : Wednesday, September 1, 2021 - 4:32:03 PM

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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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