High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice
Juliane Zemdegs1,2,3,4, Gaël Quesseveur1, David Jarriault4
1Faculté de Pharmacie, Université Paris Sud XI, Châtenay-Malabry, Cedex, France.
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.
Insights
Type 2 diabetes mellitus (T2DM) is linked to depression, with high-fat diets causing anxiety-like behaviors and altered brain serotonin. Diet reversal improved symptoms, suggesting a metabolic link to mood disorders.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Psychiatry
Background:
- The bidirectional link between type 2 diabetes mellitus (T2DM) and depression is established.
- Metabolic disorders' potential to induce psychiatric symptoms or affect antidepressant efficacy is under-investigated.
Purpose of the Study:
- To investigate the impact of T2DM on emotionality.
- To propose therapeutic strategies for depressed diabetic patients.
Main Methods:
- Mice were fed a high-fat diet (HFD) to induce metabolic and behavioral changes.
- Intra-hippocampal microdialysis assessed neurotransmitter levels.
- The effects of escitalopram and HFD withdrawal on metabolic and behavioral anomalies were evaluated.
Main Results:
- HFD-induced obesity, hyperglycemia, and glucose intolerance correlated with anxiogenic-like/depressive-like symptoms.
- Decreased hippocampal extracellular serotonin (5-HT) and increased 5-HT1A autoreceptor sensitivity were observed.
- Escitalopram efficacy was diminished in HFD-fed mice, while HFD withdrawal reversed metabolic issues and improved anxiety, though some behavioral deficits remained.
Conclusions:
- T2DM and depression are closely correlated, linked by impaired hippocampal 5-HT neurotransmission.
- Further research is needed to determine optimal treatment strategies for this comorbidity.
