ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
High-Fat Diet Induced Anxiety and Anhedonia: Impact on Brain Homeostasis and Inflammation.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.
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Who cites it
161 citing papers in PubMed, 338 citations in OpenAlex.
- Dietary Changes and Anxiety during the Coronavirus Pandemic: Differences between the Sexes.Nutrients · 2021Trial
- The role of zinc homeostasis in major depressive disorder: heterogeneous pathological mechanisms and therapeutic implications.Annals of medicine · 2026Review
- High-fat diet exposure, internal state, and reward value influence decision making during motivational conflict.Neurobiology of stress · 2026Article
- Neurobehavioral Consequences of Obesity: The Role of Inflammation.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- The distinct effects of metabolic syndrome on negative symptoms and on antipsychotic therapy of schizophrenia involve insular volume, functional connectivity, and genetic polymorphisms.Translational psychiatry · 2026Article
- Nocturnal Dim Blue Light Is Associated with Splenic Immune Dysregulation and Altered CORT-GR Signalling in High-Fat-Diet-Fed Mice.Antioxidants (Basel, Switzerland) · 2026Article
- Blunted anticipation, but not consummation, of food rewards in depression.Cell reports. Medicine · 2026Article
- Neural mechanisms linking Western diet consumption and cognitive impairment: a role for the vagus nerve.Clinical science (London, England : 1979) · 2026Review
- Complement 3a Receptor mediates high fat diet induced hypothalamic accumulation of lipid associated microglia to regulate neuroinflammation and obesity.bioRxiv : the preprint server for biology · 2026Article
- The Multifaceted Roles of GPR120 in Central Nervous System Disorders: Mechanistic Insights and Therapeutic Implications.Molecular neurobiology · 2026Review
- Impact of high-fat diet and feeding time on daily anxious-like behaviors in aged male rats.Behavioral and brain functions : BBF · 2026Article
- Chronic High-Carbohydrate And High-Fat Diet-Induced Metabolic Syndrome Leads To Adrenal Dysfunction, Altered Dendritic Morphology In Limbic Regions, And Anxiety-Like Behaviors In Male Rats.Journal of molecular neuroscience : MN · 2026Article
- Deoxycholic acid promotes anxiety- and depression-like behaviors in mice via modulation of the gut microbial metabolite indole-3-propionic acid.Frontiers in immunology · 2026Article
- [Nutritional and sedentary habits associated with suicidal behavior in Argentine adolescents: CHAID decision tree]Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina) · 2025Article
- Associations of nutritional habits, lifestyle, and demographic factors with mental health outcomes among university students in Lebanon: a cross-sectional study.BMC public health · 2025Article
- Lysine restriction attenuates obesity-related anxiety-like behaviors via increasing Oscillibacter ruminantium-mediated tryptophol regulation.Microbiome · 2025Article
- An interoceptive model of energy allostasis linking metabolic and mental health.Science advances · 2025Review
- The Impact of Biological Sex And High-Fat High-Fructose Diet on Brain Dysfunction in an Animal Model of Sepsis.Molecular neurobiology · 2025Article
- Polyunsaturated fatty-acids diet increases fear discrimination in rats and IGF-2 receptors signaling in the auditory cortex.Scientific reports · 2025Article
- Review
101 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Depression and type 2 diabetes (T2D) are highly comorbid disorders that carry a large public health burden. However, there is a clear lack of knowledge of the neural pathological pathways underlying these illnesses. The present study aims to elucidate the molecular mechanisms by which a diet rich in fat can cause multiple complications in the brain, thereby affecting intracellular signaling and gene expression that underlie anxiety and depressive behaviors. The results show that a high-fat diet (HFD; ~16 weeks) causes anxiety and anhedonic behaviors. Importantly, the results also show that 4 months of HFD causes disruption of intracellular cascades involved in synaptic plasticity and insulin signaling/glucose homeostasis (ie, Akt, extracellular signal-regulated kinase (ERK), P70S6K), as well as increased corticosterone levels and activation of the innate immune system, including elevation of inflammatory cytokines (ie, IL-6, IL-1β, TNFα). Interestingly, the rapid acting antidepressant ketamine reverses the behavioral deficits caused by HFD and activates ERK and P70S6 kinase signaling in the prefrontal cortex. In addition, we found that pharmacological blockade of the innate immune inflammasome system by repeated administration of an inhibitor of the purinergic P2X7 receptor blocks the anxiety caused by HFD. Together these studies further elucidate the signaling pathways that underlie chronic HFD exposure on anxiety and depressive behaviors, and identify novel therapeutic targets for patients with metabolic disorder or T2D who suffer from anxiety and depression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.