Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis.

Abstract:

Alzheimer's disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife increases AD risk. Furthermore, AD is associated with diabetes-like alterations in glucose metabolism. Here, we investigated metabolic features of amyloid precursor protein overexpressing APP23 female mice modeling AD upon long-term challenge with high-sucrose (HSD) or high-fat diet (HFD). Compared to wild type littermates (WT), APP23 females were less prone to mild HSD-induced and considerable HFD-induced glucose tolerance deterioration, despite unaltered glucose tolerance during normal-control diet. Indirect calorimetry revealed increased energy expenditure and hyperactivity in APP23 females. Dietary interventions, especially HFD, had weaker effects on lean and fat mass gain, steatosis and adipocyte hypertrophy of APP23 than WT mice, as shown by (1)H-magnetic-resonance-spectroscopy, histological and biochemical analyses. Proteome analysis revealed differentially regulated expression of mitochondrial proteins in APP23 livers and brains. In conclusion, hyperactivity, increased metabolic rate, and global mitochondrial dysfunction potentially add up to the development of AD-related body weight changes in APP23 females, becoming especially evident during diet-induced metabolic challenge. These findings emphasize the importance of translating this metabolic phenotyping into human research to decode the metabolic component in AD pathogenesis.

SEEK ID: https://seek.lisym.org/publications/303

PubMed ID: 33864446

Projects: LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Publication type: Journal

Journal: Aging (Albany NY)

Citation: Aging (Albany NY). 2021 Apr 16;13(8):10891-10919. doi: 10.18632/aging.202978. Epub 2021 Apr 16.

Date Published: 16th Apr 2021

Registered Mode: by PubMed ID

Authors: S. Schreyer, N. Berndt, J. Eckstein, M. Mulleder, S. Hemmati-Sadeghi, C. Klein, B. Abuelnor, A. Panzel, D. Meierhofer, J. Spranger, B. Steiner, S. Brachs

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Created: 14th May 2021 at 14:11

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