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bioRxiv · 10.1101/2021.12.21.473697

Young APPKI NL-G-F/NL-G-F mice display high-fat diet-induced metabolic disturbances and specific disorders associated with brain energy homeostasis.

Wang, W.·Tanokashira, D.·Maruyama, M.·Kuroiwa, C.·Saito, T.·Sado, T. C.·Taguchi, A.
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Abstract

AimType 2 diabetes mellitus (T2DM) is an increased risk factor for Alzheimers disease (AD); however, the relationship between the two conditions is controversial. High-fat diet (HFD) causes cognitive impairment with/without A{beta} accumulation in middle-aged or aged transgenic (Tg) and knock-in (KI) AD mouse models, except for metabolic disorders, which commonly occur in all mice types. Alternatively, whether HFD in early life impacts energy metabolism and neurological phenotypes in young AD mouse models remains unknown. In the present study, we examined the effects of HFD on young APPKI NL-G-F/NL-G-F mice, one of the novel knock-in (KI)-AD mouse models. MethodsThe mice were categorized by diet into two experimental groups, normal diet (ND) and HFD. Four-week-old WT and APPKI NL-G-F/NL-G-F mice were fed ND or HFD for nine weeks. Both types of mice on ND and HFD were examined during young adulthood. ResultsHFD causes T2DM-related metabolic disturbances in young WT and APPKI NL-G-F/NL-G-F mice and specific impairment of brain energy homeostasis only in young APPKI NL-G-F/NL-G-F mice. However, HFD-induced metabolic dysfunctions had no impact on behaviors, A{beta} levels, and specific IRS1 modifications in both young APPKI NL-G-F/NL- G-F mice and young WT mice. ConclusionHFD in early life is effective in causing metabolic disturbances in young WT and APPKI NL-G-F/NL-G-F mice but is ineffective in inducing neurological disorders in young mice, which suggests that the aging effects along with long-term HFD cause neurological alterations.

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Wang, W., Tanokashira, D., Maruyama, M., Kuroiwa, C., Saito, T., Sado, T. C., Taguchi, A.. 2021-12-23. Young APPKI NL-G-F/NL-G-F mice display high-fat diet-induced metabolic disturbances and specific disorders associated with brain energy homeostasis.. https://doi.org/10.1101/2021.12.21.473697

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