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

被引：4

作者：

Schreyer, Stefanie ^{[1
,2
,3
]}

Berndt, Nikolaus ^{[4
,5
,6
]}

Eckstein, Johannes ^{[2
,3
,7
]}

Muelleder, Michael ^{[2
,3
,8
]}

Hemmati-Sadeghi, Shabnam ^{[1
,2
,3
]}

Klein, Charlotte ^{[1
,2
,3
]}

Abuelnor, Basim ^{[1
,2
,3
]}

Panzel, Alina ^{[1
,2
,3
]}

Meierhofer, David ^{[9
]}

Spranger, Joachim ^{[2
,3
,10
,11
]}

Steiner, Barbara ^{[1
,2
,3
]}

Brachs, Sebastian ^{[2
,3
,10
,11
]}

机构：

[1] Charite Univ Med Berlin, Dept Neurol, D-10117 Berlin, Germany

[2] Free Univ Berlin, D-10117 Berlin, Germany

[3] Humboldt Univ, D-10117 Berlin, Germany

[4] Charite Univ Med Berlin, Inst Imaging Sci & Computat Modelling Cardiovasc, D-13353 Berlin, Germany

[5] Free Univ Berlin, D-13353 Berlin, Germany

[6] Humboldt Univ, D-13353 Berlin, Germany

[7] Charite Univ Med Berlin, Inst Biochem, D-10117 Berlin, Germany

[8] Charite Univ Med Berlin, Core Facil High Throughput Mass Spectrometry, D-10117 Berlin, Germany

[9] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

[10] Charite Univ Med Berlin, Dept Endocrinol & Metab, D-10117 Berlin, Germany

[11] DZHK German Ctr Cardiovasc Res, Partner Site Berlin, Berlin, Germany

来源：

AGING-US | 2021年 / 13卷 / 08期

关键词：

Alzheimer' s disease; diet-induced obesity; hypertrophy; energy expenditure; steatosis; APP23 TRANSGENIC MICE; WEIGHT-LOSS; INSULIN SENSITIVITY; BODY-MASS; DISEASE; BETA; DIAGNOSIS; LIPOLYSIS; DEMENTIA; MODEL;

D O I：

10.18632/aging.202978

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 longterm 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 1H-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.

引用

页码：10891 / 10919

页数：29