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Tissue-Specific Metabolomics Analysis Identifies the Liver as a Major Organ of Metabolic Disorders in Amyloid Precursor Protein/Presenilin 1 Mice of Alzheimer's Disease.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2019-01-09 , DOI: 10.1021/acs.jproteome.8b00847
Hong Zheng 1 , Aimin Cai 1 , Qi Shu 1 , Yan Niu 1 , Pengtao Xu 1 , Chen Li 1 , Li Lin 2 , Hongchang Gao 1
Affiliation  

Alzheimer's disease (AD) is regarded as a metabolic disorder, and more attention has been paid to brain metabolism. However, AD may also affect metabolism in the peripheral organs beyond the brain. In this study, therefore, we investigated metabolic changes in the liver, kidney, and heart of amyloid precursor protein/presenilin 1 (APP/PS1) mice at 1, 5, and 10 months of age by using 1H NMR-based metabolomics and chemometrics. Metabolomic results reveal that the liver was the earliest affected organ in APP/PS1 mice during amyloid pathology progression, followed by the kidney and heart. Moreover, a hypometabolic state was found in the liver of APP/PS1 mice at 5 months of age, and the disturbed metabolites were mainly involved in energy metabolism, amino acid metabolism, nucleic acid metabolism, as well as ketone and fatty acid metabolism. In conclusion, our results suggest that AD is a systemic metabolic dysfunction, and hepatic metabolic abnormality may reflect amyloid pathology progression.

中文翻译:

组织特定的代谢组学分析鉴定为淀粉样前体蛋白/早老素1小鼠的阿尔茨海默氏病小鼠的代谢紊乱的主要器官。

阿尔茨海默氏病(AD)被认为是一种代谢性疾病,人们对脑代谢的关注也越来越多。但是,AD也可能影响大脑以外的周围器官的新陈代谢。因此,在这项研究中,我们使用基于1H NMR的代谢组学和化学计量学方法研究了1、5和10个月大时淀粉样蛋白前体蛋白/早老素1(APP / PS1)小鼠肝脏,肾脏和心脏的代谢变化。代谢组学研究结果表明,在淀粉样蛋白病理变化过程中,肝脏是APP / PS1小鼠中受影响最早的器官,其次是肾脏和心脏。此外,在APP / PS1小鼠的5个月大时,其肝脏处于低代谢状态,代谢紊乱主要涉及能量代谢,氨基酸代谢,核酸代谢以及酮和脂肪酸代谢。
更新日期:2019-02-07
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