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Cited by 54Alzheimer's disease research and treatmentsDiet, Metabolism, and DiseaseAdipokines, Inflammation, and Metabolic Diseases

Metabolic disturbances of a high-fat diet are dependent on APOE genotype and sex.

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Jones, Nahdia S., Watson, Katarina Q., Rebeck, G. William·2019·eneuro
DOI 10.1523/eneuro.0267-19.2019PMC PMC6795556
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Abstract

Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for Alzheimer’s disease (AD).APOE4 is also associated with an increased risk of metabolic syndrome. Obesity is a major environmental risk factor for AD. While APOE genotype and obesity independently affect metabolism and cognition, they may also have synergistic effects. Here, we examined the metabolic and behavioral alterations associated with a high-fat diet (HFD) in male and female APOE knock-in mice. Male and female mice were fed a 45% kcal HFD or a 10% kcal low-fat diet (LFD) for 12 weeks and adipose tissue accumulation, glucose levels, anxiety-like behavior, and spatial memory were examined. We found that with HFD, male APOE4 mice were more susceptible to metabolic disturbances, including visceral adipose tissue (VAT) accumulation and glucose intolerance when compared to APOE3 mice, while female APOE3 and APOE4 mice had similar metabolic responses. Behaviorally, there were no effects of HFD in mice of either genotype. Our results suggest that metabolic responses to HFD are dependent on both sex and APOE genotype.

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  • Addition of a high fat/high sugar diet exacerbates Alzheimer's disease phenotypes in mouse models relevant to early-onset AD.

    “Also, the addition of an HFD exacerbated AD phenotypes in mouse models relevant to early-onset AD (Knight et al., 2014; Jones et al., 2019; Bracko et al., 2020; Robison et al., 2020; Jones et al., 2021).”

    From Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice (2022) · cites this paper as Jones et al., 2019

    The Discussion (page unavailable) reports that high-fat diets worsened cognitive deficits or AD pathology in some AD mouse models, which supports the general point. But this paper studied APOE knock-in mice, not an early-onset AD model, and found no robust diet-related behavioral effects in its own experiment. The cited passages also do not establish a high-sugar diet. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • With HFD, male APOE4 mice were more susceptible to metabolic disturbances, including glucose intolerance, compared to APOE3 mice.

    “In one study, Jones et al. (2019) found that with HFD, male APOE4 mice were more susceptible to metabolic disturbances, including glucose intolerance when compared to APOE3 mice.”

    From Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice (2022) · cites this paper as Jones et al., 2019

  • Behavioral deficits were not observed due to HFD, suggesting that metabolic responses to HFD are dependent on both sex and APOE genotype.

    “Behavioral deficits were not observed due to HFD, suggesting that metabolic responses to HFD are dependent on both sex and APOE genotype.”

    From Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice (2022) · cites this paper as Jones et al., 2019

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Cited by

Sorted by citations

Authors
Jones, N. S., Watson, K. Q., & Rebeck, G. W.
Affiliations
Georgetown University (US)
Corresponding author
Rebeck, G. William
ORCID
Venue
eneuro
Publisher
Society for Neuroscience
Published
2019-09
Volume
6
Issue
5
Pages
ENEURO.0267-19.2019
ISSN
2373-2822 (ISSN-L)
DOI
10.1523/eneuro.0267-19.2019
PMC
PMC6795556
OpenAlex
W2976687323
Cited by
54
References
8
Citations by year
2026: 4 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 12 · 2020: 5 · 2019: 2 · 2018: 2
FWCI
4.63
Type
journal article
Language
en
Open access
Licence
Locations
  • eNeuro (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
HHS | NIH | National Institute of Neurological Disorders and Stroke (R01 NS10070-03, R01 NS100704-S2)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
APOE ε4, APOE genotype, high-fat diet, Alzheimer's disease risk, metabolic syndrome, obesity, sex differences, visceral adipose tissue, impaired glucose tolerance, anxiety-like behavior, spatial memory
MeSH terms
Animals, Apolipoproteins E, Behavior, Animal, Female, Genotype, Insulin Resistance, Male, Mice, Inbred C57BL, Obesity, Sex Factors, Metabolic Syndrome, Intra-Abdominal Fat, Mice, Gene Knock-In Techniques, Diet, High-Fat

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