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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.

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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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.

How this study connects

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