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
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
复制标题
组织特异性代谢组学分析确定肝脏是淀粉样前体蛋白/早老素 1 阿尔茨海默病小鼠代谢紊乱的主要器官
DOI：
10.1021/acs.jproteome.8b00847
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发表时间：
2019
影响因子：
4.4
通讯作者：
Gao Hongchang
中科院分区：
文献类型：
--
作者：
Zheng Hong;Cai Aimin;Shu Qi;Niu Yan;Xu Pengtao;Li Chen;Lin Li;Gao Hongchang
阿尔茨海默病（AD）被认为是一种代谢性疾病，脑代谢受到更多关注。然而，AD 也可能影响大脑以外的周围器官的新陈代谢。因此，在本研究中，我们利用基于 1 H NMR 的代谢组学和化学计量学研究了 1、5 和 10 个月龄淀粉样前体蛋白/早老素 1 (APP/PS1) 小鼠的肝脏、肾脏和心脏的代谢变化。代谢组学结果显示，在淀粉样蛋白病理进展过程中，APP/PS1 小鼠的肝脏是最早受影响的器官，其次是肾脏和心脏。此外，5月龄时APP/PS1小鼠肝脏出现代谢低下状态，紊乱的代谢物主要涉及能量代谢、氨基酸代谢、核酸代谢以及酮和脂肪酸代谢。总之，我们的结果表明AD是一种全身代谢功能障碍，肝脏代谢异常可能反映了淀粉样蛋白的病理进展。
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 using1H 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.