Does a high-fat diet hit APOE4 males harder?
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.
Source
Metabolic Disturbances of a High-Fat Diet Are Dependent on APOE Genotype and Sex
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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What they did
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.
What they found
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.
The limits
What it doesn't show
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.
Key terms
- APOE4
- Apolipoprotein E ε4 allele; strongest common genetic risk factor for late-onset Alzheimer’s disease.
- HFD / LFD
- 45% kcal fat Research Diets D12451 versus ingredient-matched 10% kcal fat D12450H.
- VAT
- Visceral adipose tissue quantified on abdominal MRI.
- GTT
- Glucose tolerance test after 12 weeks of diet.
- Barnes maze
- Spatial memory assay used with open field and elevated zero maze.
- Knock-in mice
- Mice expressing human APOE3 or APOE4 on a C57BL/6J background.
Flashcards
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The high-fat diet was:
Common questions
How long was the diet?
12 weeks starting at six months of age.
Which mice were metabolically most vulnerable?
Male APOE4 mice (VAT and glucose intolerance vs APOE3).
Did HFD change behavior?
No effects of HFD in mice of either genotype.
What fat percentages were used?
45% kcal HFD versus 10% kcal matched LFD.
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