ArticleNeurobiology of disease2014
High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice.
Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 1 of them a synthesis that pooled it.
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Who cites it
178 citing papers in PubMed, 1 synthesis or guideline pooled it, 303 citations in OpenAlex.
- Effects of dietary fat manipulation on cognition in mice and rats: protocol for a systematic review and meta-analysis.BMJ open science · 2020Pooled it
- Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial.JAMA neurology · 2019Trial
- Effects of obesity on brain health and cognition.Nature reviews. Neurology · 2026Review
- PQBP1-dependent alternative RNA splicing underlies high calorie diet-induced cognitive impairment.Molecular psychiatry · 2026Article
- Microbiota-Gut-Brain Axis Mechanisms in Cognitive Impairment Associated with Central Obesity.Current obesity reports · 2026Review
- 8-Gingerol Mitigates MPPNeurochemical research · 2026Article
- Neuroprotective effects of hydrogen sulfide on BDNF, IGF-1, and oxidative stress in the hippocampus of high-fat diet rats.IBRO neuroscience reports · 2026Article
- Obesity-driven phosphatidylethanolamine dysregulation impairs neuroimmune crosstalk and accelerates Alzheimer's pathogenesis.Molecular neurodegeneration · 2026Article
- Narrative Review "Dual Frontiers in Neurodegeneration: Pharmacological Synergies and Divergences in Parkinson's Disease and Type 2 Diabetes Mellitus".Cellular and molecular neurobiology · 2026Review
- High-fat diet attenuates estradiol's efficacy on cognitive function and hippocampal synaptic plasticity in middle-aged ovariectomized mice.Physiological reports · 2026Article
- The Double-Edged Sword of Gestational Insulin Resistance: Navigating Maternal Adaptation and Its Risks for Pregnancy and Offspring Health.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Brain lipid profiles and oligodendrocyte gene expression show discordant responses to high-fat diet in Alzheimer's disease mice.Scientific reports · 2026Article
- Article
- High‑fat diet and cognitive dysfunction: Mechanistic insights into diet‑induced neurodegeneration (Review).International journal of molecular medicine · 2026Review
- Article
- Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline.Diseases (Basel, Switzerland) · 2025Review
- Association of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program.Communications biology · 2025Article
- Cognitive Dysfunction and Dementia in Type 2 Diabetes Mellitus: Insights into Mechanisms, Models, and Therapeutics.ACS pharmacology & translational science · 2025Review
- Brain insulin resistance mediated cognitive impairment and neurodegeneration: Type-3 diabetes or Alzheimer's Disease.Acta neurologica Belgica · 2025Review
- High-Intensity Interval Training Improves Memory Deficits in Obese Mice by Enhancing Osteocalcin-Driven Astrocytic BDNF Expression and Stimulating Hippocampal Neurogenesis.Neurochemical research · 2025Article
118 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17days or a moderate high fat diet (HFD, 45% kcal by fat) for 8weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS(616)), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors.
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