ArticleNutrients2020
Metabolic Defects Caused by High-Fat Diet Modify Disease Risk through Inflammatory and Amyloidogenic Pathways in a Mouse Model of Alzheimer's Disease.
Article in Nutrients, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Regulation of gut microbiome by ketogenic diet in neurodegenerative diseases: A molecular crosstalk.Frontiers in aging neuroscience · 2022Pooled it
- Obesity-driven phosphatidylethanolamine dysregulation impairs neuroimmune crosstalk and accelerates Alzheimer's pathogenesis.Molecular neurodegeneration · 2026Article
- PLCG2 signaling and genetic resilience in Alzheimer's disease.Molecular neurodegeneration · 2026Review
- Ethanol exposure and high-fat diet: assessing the neuroimmune and metabolic mechanisms in Alzheimer's disease pathology.Frontiers in neuroscience · 2026Review
- The Role of Supraoptic Hypothalamic Arginine Vasopressin Neurons in Aging-Associated Water Balance and Thermoregulatory Deficits.bioRxiv : the preprint server for biology · 2025Article
- Decoding adipose-brain crosstalk: Distinct lipid cargo in human adipose-derived extracellular vesicles modulates amyloid aggregation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- High-Fat Diet-Induced Excessive Accumulation of Cerebral Cholesterol Esters and Microglial Dysfunction Exacerbate Alzheimer's Disease Pathology in APPMolecular neurobiology · 2025Article
- The Impact of the Exposome on Alzheimer's Disease: The Influence of Nutrition.International journal of molecular sciences · 2025Review
- TBG096 Ameliorates Memory Deficiency in AD Mouse Model via Promoting Neurogenesis and Regulation of Hsc70/HK2/PKM2/LAMP2A Signaling Pathway.International journal of molecular sciences · 2025Article
- Mitigation of Atherosclerotic Vascular Damage and Cognitive Improvement Through Mesenchymal Stem Cells in an Alzheimer's Disease Mouse Model.International journal of molecular sciences · 2024Article
- Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer's disease.Brain, behavior, and immunity · 2024Article
- Sex-dependent effects of carbohydrate source and quantity on caspase-1 activity in the mouse central nervous system.Journal of neuroinflammation · 2024Article
- The impacts of sex and the 5xFAD model of Alzheimer's disease on the sleep and spatial learning responses to feeding time.Frontiers in neurology · 2024Article
- High caloric intake improves neuronal metabolism and functional hyperemia in a rat model of early AD pathology.Theranostics · 2024Article
- Article
- A novel rhein-huprine hybrid ameliorates disease-modifying properties in preclinical mice model of Alzheimer's disease exacerbated with high fat diet.Cell & bioscience · 2023Article
- The effect of dietary fat consumption on Alzheimer's disease pathogenesis in mouse models.Translational psychiatry · 2022Review
- The Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer's Disease.International journal of molecular sciences · 2022Review
- PLCG2 is associated with the inflammatory response and is induced by amyloid plaques in Alzheimer's disease.Genome medicine · 2022Article
- Effects of Herbal Therapy on Intestinal Microbiota and Serum Metabolomics in Different Rat Models of Mongolian Medicine.Evidence-based complementary and alternative medicine : eCAM · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
High-fat diet (HFD) has been shown to accelerate Alzheimer's disease (AD) pathology, but the exact molecular and cellular mechanisms remain incompletely understood. Moreover, it is unknown whether AD mice are more susceptible to HFD-induced metabolic dysfunctions. To address these questions, we used 5xFAD mice as an Alzheimer's disease model to study the physiological and molecular underpinning between HFD-induced metabolic defects and AD pathology. We systematically profiled the metabolic parameters, the gut microbiome composition, and hippocampal gene expression in 5xFAD and wild type (WT) mice fed normal chow diet and HFD. HFD feeding impaired energy metabolism in male 5xFAD mice, leading to increased locomotor activity, energy expenditure, and food intake. 5xFAD mice on HFD had elevated circulating lipids and worsened glucose intolerance. HFD caused profound changes in gut microbiome compositions, though no difference between genotype was detected. We measured hippocampal mRNAs related to AD neuropathology and neuroinflammation and showed that HFD elevated the expression of apoptotic, microglial, and amyloidogenic genes in 5xFAD mice. Pathway analysis revealed that differentially regulated genes were involved in insulin signaling, cytokine signaling, cellular stress, and neurotransmission. Collectively, our results showed that 5xFAD mice were more susceptible to HFD-induced metabolic dysregulation and suggest that targeting metabolic dysfunctions can ameliorate AD symptoms via effects on insulin signaling and neuroinflammation in the hippocampus.
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What OpenQuestion holds
Registered trials
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.