ArticleJournal of neuroinflammation2021
High-fat diet increases gliosis and immediate early gene expression in APOE3 mice, but not APOE4 mice.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Older adult APOE4 mice exhibit modest immunometabolic adaptation following microglial APOE2 replacement.Neurobiology of aging · 2026Article
- Single-cell RNA sequencing uncovers molecular features underlying microglial lipid accumulation and depression-related behaviors in high-fat diet mouse model of obesity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Association between apolipoprotein E gene polymorphisms and the effects of high-intensity interval training on body composition in university students.Frontiers in nutrition · 2026Article
- Obesity is associated with increased brain glucose uptake and activity but not neuroinflammation (TSPO availability) in monozygotic twin pairs discordant for BMI-Exercise training reverses increased brain activity.Diabetes, obesity & metabolism · 2025Article
- APOE4 rat model of Alzheimer's disease: sex differences, genetic risk and diet.BMC neuroscience · 2024Article
- Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation.International journal of molecular sciences · 2024Review
- Sex-dependent effects of carbohydrate source and quantity on caspase-1 activity in the mouse central nervous system.Journal of neuroinflammation · 2024Article
- Obesity affects brain cortex gene expression in an APOE genotype and sex dependent manner.International journal of obesity (2005) · 2024Article
- Identification of lncRNA-miRNA-mRNA Networks in the Lenticular Nucleus Region of the Brain Contributes to Hepatolenticular Degeneration Pathogenesis and Therapy.Molecular neurobiology · 2024Article
- Effects of obesogenic diet and 17β-estradiol in female mice withFrontiers in aging neuroscience · 2024Article
- Circadian Regulation of Apolipoproteins in the Brain: Implications in Lipid Metabolism and Disease.International journal of molecular sciences · 2023Review
- Apolipoprotein E in lipid metabolism and neurodegenerative disease.Trends in endocrinology and metabolism: TEM · 2023Review
- Age, sex, and apolipoprotein E isoform alter contextual fear learning, neuronal activation, and baseline DNA damage in the hippocampus.Molecular psychiatry · 2023Article
- Effects ofMetabolites · 2023Article
- Obesogenic Diet-Induced Neuroinflammation: A Pathological Link between Hedonic and Homeostatic Control of Food Intake.International journal of molecular sciences · 2023Review
- Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes.Metabolites · 2023Review
- Sex and diet-dependent gene alterations in human and rat brains with a history of nicotine exposure.Frontiers in psychiatry · 2023Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Independent APOE4 knock-in mouse models display reduced brain APOE protein, altered neuroinflammation, and simplification of dendritic spines.Journal of neurochemistry · 2022Article
- APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases.Molecular neurodegeneration · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAPOE4 is the strongest genetic risk factor for Alzheimer's disease (AD), and obesity is a strong environmental risk factor for AD. These factors result in multiple central nervous system (CNS) disturbances and significantly increase chances of AD. Since over 20% of the US population carry the APOE4 allele and over 40% are obese, it is important to understand how these risk factors interact to affect neurons and glia in the CNS.
methodsWe fed male and female APOE3 and APOE4 knock-in mice a high-fat diet (HFD-45% kcal fat) or a "control" diet (CD-10% kcal fat) for 12 weeks beginning at 6 months of age. At the end of the 12 weeks, brains were collected and analyzed for gliosis, neuroinflammatory genes, and neuronal integrity.
resultsAPOE3 mice on HFD, but not APOE4 mice, experienced increases in gliosis as measured by GFAP and Iba1 immunostaining. APOE4 mice on HFD showed a stronger increase in the expression of Adora2a than APOE3 mice. Finally, APOE3 mice on HFD, but not APOE4 mice, also showed increased neuronal expression of immediate early genes cFos and Arc.
conclusionsThese findings demonstrate that APOE genotype and obesity interact in their effects on important processes particularly related to inflammation and neuronal plasticity in the CNS. During the early stages of obesity, the APOE3 genotype modulates a response to HFD while the APOE4 genotype does not. This supports a model where early dysregulation of inflammation in APOE4 brains could predispose to CNS damages from various insults and later result in the increased CNS damage normally associated with the APOE4 genotype.
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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 Socratic graph.