Abstract
Objective: 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. Methods: 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. Results: We found that with HFD, male APOE4 mice were more susceptible to metabolic disturbances, including visceral adipose tissue 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. Conclusions: Our results suggest that metabolic responses to HFD are dependent on both sex and APOE genotype.
Significance StatementAPOE4 and obesity are independently associated with increased risk of metabolic syndrome and cognitive impairment. Obesity may cause greater metabolic and cognitive disturbances in APOE4 carriers. However, the metabolic and cognitive effects of obesity on male and female APOE4 carriers remain unknown. Here we examine and compare the metabolic and cognitive disturbances caused by a high fat diet in both male and female APOE3 and APOE4 mice. Through this study, we examine how high fat diet affects the APOE3 and APOE4 genotype and how these effects differ across sexes.
Footnotes
The authors declare no competing financial interests.
This work was funded by NIH R01 NS100704 and NS100704-S1sss.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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