High fat diet-induced obesity leads to depressive and anxiety-like behaviors in mice via AMPK/mTOR-mediated autophagy

Li, Yong; Cheng, Yujie; Zhou, Yuan; Du, Hongmei; Zhang, Cui; Zhao, Zhentao; Chen, Yuenan; Zhou, Zhongnan; Mei, Jinyu; Wu, Wen Li; Chen, Ming

doi:10.1016/j.expneurol.2021.113949

Cited by 66 publications

(35 citation statements)

References 81 publications

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“…Our data showed that microglial density, soma area, territory area, and CD68 expression in the ventral hippocampus were significantly increased in HFD-fed adolescent mice. Consistent with our results, it was found that in adult animals, the number and total process length of microglia in the hippocampal DG region are increased after HFD feeding for one month [ 73 ] and that microglia in these animals are distinct from traditional amoeba-like activated microglia [ 68 ]. Because microglial processes continually contact newborn neurons and play a functionally dynamic role in hippocampal neurogenesis, increases in microglial density, soma area, territory area, and CD68 expression in HFD-fed adolescent mice might indicate that the basal activity of microglia and their connections with adjacent cells are increased after HFD consumption in adolescence.…”

Section: Discussionsupporting

confidence: 90%

High-Fat Diet Consumption in Adolescence Induces Emotional Behavior Alterations and Hippocampal Neurogenesis Deficits Accompanied by Excessive Microglial Activation

Yao

Yang

Wang

et al. 2022

IJMS

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Adolescence is a developmental epoch characterized by massive neural circuit remodeling; thus, the brain is particularly vulnerable to environmental influences during this period. Excessive high-fat diet (HFD) consumption, which is very common among adolescents, has long been recognized as a potent risk factor for multiple mood disorders, including depression and anxiety. However, the precise mechanisms underlying the influences of HFD consumption in adolescence on emotional health are far from clear. In the present study, C57BL/6 mice were fed a control diet (CD) or HFD for about 4 weeks from postnatal day (P) 28 to P60, spanning most of the adolescence period, and then subjected to behavioral assessments and histological examinations. HFD mice exhibited elevated levels of depression and anxiety, decreased hippocampal neurogenesis, and excessive microglial activation in the ventral hippocampus. Furthermore, in HFD-fed mice, microglia showed increased DCX+ inclusions, suggesting aberrant microglial engulfment of newborn neurons in HFD-fed adolescents. To our knowledge, this is the first observation suggesting that the negative effects of HFD consumption in adolescence on emotion and neuroplasticity may be attributed at least in part to aberrant microglial engulfment of nascent neurons, extending our understanding of the mechanism underlying HFD-related affective disorders in young people.

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Section: Discussionsupporting

confidence: 90%

High-Fat Diet Consumption in Adolescence Induces Emotional Behavior Alterations and Hippocampal Neurogenesis Deficits Accompanied by Excessive Microglial Activation

Yao

Yang

Wang

et al. 2022

IJMS

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“…The study of Vagena et al showed that HFD promoted depression-like behaviors in mice via suppressing hypothalamic protein kinase A ( Vagena et al, 2019 ). In addition, Li et al found that HFD-induced obesity resulted in depressive and anxiety-like behaviors in mice via AMPK/mTOR-mediated autophagy ( Li et al, 2022a ). Those are complementary evidences to our study and reinforce the current model of HFD-induced depressive-like behaviors.…”

Section: Discussionmentioning

confidence: 99%

Inflammation-activated C/EBPβ mediates high-fat diet-induced depression-like behaviors in mice

Chen

Wang

et al. 2022

Front. Mol. Neurosci.

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Depression, one of the most common causes of disability, has a high prevalence rate in patients with metabolic syndrome. Type 2 diabetes patients are at an increased risk for depression. However, the molecular mechanism coupling diabetes to depressive disorder remains largely unknown. Here we found that the neuroinflammation, associated with high-fat diet (HFD)-induced diabetes and obesity, activated the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) in hippocampal neurons. This factor repressed brain-derived neurotrophic factor (BDNF) expression and caused depression-like behaviors in male mice. Besides, the loss of C/EBPβ expression in C/EBPβ heterozygous knockout male mice attenuated HFD-induced depression-like behaviors, whereas Thy1-C/EBPβ transgenic male mice (overexpressing C/EBPβ) showed depressive behaviors after a short-term HFD. Furthermore, HFD impaired synaptic plasticity and decreased surface expression of glutamate receptors in the hippocampus of wild-type (WT) mice, but not in C/EBPβ heterozygous knockout mice. Remarkably, the anti-inflammatory drug aspirin strongly alleviated HFD-elicited depression-like behaviors in neuronal C/EBPβ transgenic mice. Finally, the genetic delivery of BDNF or the pharmacological activation of the BDNF/TrkB signaling pathway by 7,8-dihydroxyflavone reversed anhedonia in a series of behavioral tests on HFD-fed C/EBPβ transgenic mice. Therefore, our findings aim to demonstrate that the inflammation-activated neuronal C/EBPβ promotes HFD-induced depression by diminishing BDNF expression.

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“…Based on this, the brain is highly vulnerable to functional impairment from nutrient imbalances, influencing the development and progression of psychiatric disorders. Several reports have confirmed that excessive intake of saturated fats and refined carbohydrates promotes defective behaviors and susceptibility to mental disorders in both animal models and humans (Fatemi et al, 2020;Y. Li et al, 2022;Łojko et al, 2018;Quirk et al, 2013;Zemdegs et al, 2016).…”

Section: Die T Modul Ate S Cer Amide S Me Tabolis M and Suscep Tib Il...mentioning

confidence: 92%

Contribution of ceramides metabolism in psychiatric disorders

Bernal-Vega

García-Juárez

Camacho‐Morales

2023

Journal of Neurochemistry

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Psychiatric disorders affect 970 million people worldwide, representing a significant source of disability. Although the underlying neurobiological traits for these disorders are not fully understood, a complex interplay between psychological, environmental, and biological factors contributes to their outcomes. Recent advances in lipidomic analysis and artificial intelligence algorithms have improved the identification of selective lipid species modulating the susceptibility to mental disorders. Sphingolipids (SLs) and ceramides‐related SLs are among the most abundant lipids species in the brain that support major key pathways during neurodevelopment and brain plasticity. High levels of ceramides in plasma and brain contribute to psychiatric illness susceptibility in humans and animal models. However, the neuropathological mechanism regarding the involvement of ceramides in these disorders remain inconclusive. The brain is highly susceptible to nutritional insults, which could lead to functional impairment and influence the development and progression of psychiatric disorders. While the brain relies on glucose metabolism to support its physiological needs, a selective nutrient formula appears to have greater effects on brain health than others. For instance, consumption of high‐energy diets is associated with brain anatomical, physiological, and metabolic changes, including ceramides metabolism. Herein, we will address the contribution of ceramides metabolism as a modulator of major psychiatric disorders such as depression, anxiety, bipolar disorder, schizophrenia, and attention deficit‐hyperactivity disorder. We will also describe molecular and cellular targets of ceramides metabolism assisting the maintenance and progression of psychiatric disorders and their modulation by dietary formulas as non‐pharmacologic treatments.

show abstract

High fat diet-induced obesity leads to depressive and anxiety-like behaviors in mice via AMPK/mTOR-mediated autophagy

Cited by 66 publications

References 81 publications

High-Fat Diet Consumption in Adolescence Induces Emotional Behavior Alterations and Hippocampal Neurogenesis Deficits Accompanied by Excessive Microglial Activation

High-Fat Diet Consumption in Adolescence Induces Emotional Behavior Alterations and Hippocampal Neurogenesis Deficits Accompanied by Excessive Microglial Activation

Inflammation-activated C/EBPβ mediates high-fat diet-induced depression-like behaviors in mice

Contribution of ceramides metabolism in psychiatric disorders

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