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Neurodegeneration

Does a high-fat diet hit APOE4 males harder?

Jones NS, Watson KQ, Rebeck GW · eNeuro · 2019

Open access · cc by · source: Europe PMC

In APOE knock-in mice, 12 weeks of 45% fat diet produced more visceral fat and glucose intolerance in male APOE4 than APOE3 mice, while females of both genotypes responded similarly and behavior did not change.

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How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • SupportsNeurodegenerative Biomarkersconcept

    The genotype effect existed only in one sex, and the cognitive outcomes were null in both.

    Risk genotype effects depend on sex in ways a main-effect analysis would miss. On a high-fat diet, male APOE4 mice were more susceptible to visceral fat accumulation and glucose intolerance than male APOE3 mice, while female APOE3 and APOE4 mice responded similarly — with no diet effects on anxiety-like behaviour or spatial memory in either genotype.

    Evidence for the claim as stated.

Study at a glance

Design
Animal / in-vitro — Diet-induced obesity in human APOE3 vs APOE4 knock-in mice; both sexes; HFD vs matched LFD for 12 weeks with GTT, MRI adiposity, and behavior
N
N=48 · n = 5–9/sex across APOE3/APOE4 × HFD/LFD cells (GraphPad N = 5–9)
Population
Six-month-old male and female human APOE3 and APOE4 knock-in mice on C57BL/6J
Outcome
Weight gain, glucose tolerance, MRI VAT/SAT/BAT, open field, elevated zero maze, Barnes maze

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Does a high-fat diet hit APOE4 males harder?

These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.

n = 5–9/sex; 45% vs 10% kcal fat for 12 weeks from six months of age.

Male and female human APOE3 and APOE4 knock-in mice on a C57BL/6J background ( n = 5–9/sex; the gift of Patrick Sullivan) were fed either a HFD (45% kcal fat, Research Diets-D12451) or ingredient matched low-fat diet (LFD; 10% kcal fat, Research Diets-D12450H) for 12 weeks beginning at six months of age.

Male APOE4 HFD mice weighed more than LFD APOE4 (p < 0.0001).

HFD APOE4 mice did weigh significantly more than LFD APOE4 mice ( p < 0.0001).
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Key findings

HFD groups gained more weight than LFD. Male APOE4 mice were more susceptible to VAT accumulation and glucose intolerance than male APOE3 mice; female APOE3 and APOE4 mice had similar metabolic responses. No HFD effects on anxiety-like behavior or spatial memory in either genotype.

Methodology

Fed 6-month-old male and female APOE3 and APOE4 knock-in mice (n = 5–9/sex) a 45% kcal HFD or matched 10% kcal LFD for 12 weeks, then ran GTT, abdominal/neck MRI, open field, elevated zero maze, and Barnes maze.

Limitations

A 12-week mouse diet study cannot prove that APOE4 men will develop diabetes or dementia from high-fat food, and null behavior results do not rule out longer or different cognitive assays.

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