ArticleInternational journal of obesity (2005)2024
Obesity affects brain cortex gene expression in an APOE genotype and sex dependent manner.
Article in International journal of obesity (2005), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Obesity-induced cognitive impairment: Underlying mechanisms and therapeutic prospects.Metabolism open · 2026Review
- Association between apolipoprotein E gene polymorphisms and the effects of high-intensity interval training on body composition in university students.Frontiers in nutrition · 2026Article
- Cell- and sex-specificity in the transcriptomic response of the hippocampal neurovascular unit to obesity.Communications biology · 2025Article
- Effects of obesity on aging brain and cognitive decline: A cohort study from the UK Biobank.IBRO neuroscience reports · 2025Article
- Effects of obesogenic diet and 17β-estradiol in female mice withFrontiers in aging neuroscience · 2024Article
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Authors and funding
3 authors.
Funding
Abstract
objectiveObesity is the top modifiable risk factor for Alzheimer's disease. We hypothesized that high fat diet (HFD)-induced obesity alters brain transcriptomics in APOE-genotype and sex dependent manners. Here, we investigated interactions between HFD, APOE, and sex, using a knock-in mouse model of the human APOE3 and APOE4 alleles.
methodsSix-month-old APOE3-TR and APOE4-TR mice were treated with either HFD or control chow. After 4 months, total RNA was extracted from the cerebral cortices and analyzed by poly-A enriched RNA sequencing on the Illumina platform.
resultsFemale mice demonstrated profound HFD-induced transcriptomic changes while there was little to no effect in males. In females, APOE3 brains demonstrated about five times more HFD-induced transcriptomic changes (399 up-regulated and 107 down-regulated genes) compared to APOE4 brains (30 up-regulated and 60 down-regulated). Unsupervised clustering analysis revealed two gene sets that responded to HFD in APOE3 mice but not in APOE4 mice. Pathway analysis demonstrated that HFD in APOE3 mice affected cortical pathways related to feeding behavior, blood circulation, circadian rhythms, extracellular matrix, and cell adhesion.
conclusionsFemale mice and APOE3 mice have the strongest cortical transcriptomic responses to HFD related to feeding behavior and extracellular matrix remodeling. The relative lack of response of the APOE4 brain to stress associated with obesity may leave it more susceptible to additional stresses that occur with aging and in AD.
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