Untargeted Metabolomic Profiling of Liver in a Chronic Intermittent Hypoxia Mouse Model.
Untargeted Metabolomic Profiling of Liver in a Chronic Intermittent Hypoxia Mouse Model.
复制标题
慢性间歇性缺氧小鼠模型中肝脏的非靶向代谢组学分析
DOI：
10.3389/fphys.2021.701035
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发表时间：
2021
影响因子：
4
通讯作者：
Lin XJ
中科院分区：
文献类型：
--
作者：
Chen LD;Huang ZW;Huang YZ;Huang JF;Zhang ZP;Lin XJ
阻塞性睡眠呼吸暂停(OSA)已被证明与肝脏损伤有关。然而，到目前为止，将这两种疾病联系在一起的机制在很大程度上还没有被探索出来。本研究基于UHPLC/Q-TOF MS平台，研究慢性间歇性低氧(CIH)小鼠肝脏代谢组谱，以确定改变的代谢物和相关的代谢途径。将C57BL/6小鼠(每组12只)置于间歇性低氧或对照条件(室内空气)中12周。在暴露结束时，评估肝酶和组织学变化。采用UHPLC/Q-TOF MS非靶向代谢组学方法和正交偏最小二乘判别分析(OPLS-DA)筛选小鼠肝脏代谢产物。生物信息学分析用于确定相关的代谢途径。CIH对小鼠有明显的肝损伤作用。两组间共鉴定出27种负离子模式的差异代谢物和44种阳离子模式的差异代谢物。这些代谢物涉及多种生物和代谢过程，包括各种氨基酸代谢、膜转运、脂代谢、碳水化合物代谢、核苷酸代谢、铁下垂等，在铁下垂途径中发现了谷胱甘肽、谷胱甘肽二硫化物和花生四烯酸(无过氧化)三种差异代谢物。CIH与小鼠肝脏代谢特征的显著变化有关。氨基酸代谢、膜转运、脂代谢、碳水化合物代谢、核苷酸代谢、铁下垂等代谢产物在CIH肝损伤中起重要作用。这些发现有助于更好地了解OSA与肝损伤之间的联系机制，并有助于确定潜在的治疗靶点。
Obstructive sleep apnea (OSA) has been demonstrated to be associated with liver injury. Nevertheless, the mechanisms linking the two disorders remain largely unexplored to date. Based on UHPLC/Q-TOF MS platform, the present study aimed to study the hepatic metabolomic profiling in a chronic intermittent hypoxia (CIH) mouse model to identify altered metabolites and related metabolic pathways. C57BL/6 Mice (n = 12 each group) were exposed to intermittent hypoxia or control conditions (room air) for 12 weeks. At the end of the exposure, liver enzymes and histological changes were assessed. Untargeted metabolomics approach by UHPLC/Q-TOF MS and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to screen altered metabolites in mice liver. Bioinformatics analyses were applied to identify the related metabolic pathways. CIH treatment caused a remarkable liver injury in mice. A total of 27 differential metabolites in negative ion mode and 44 in positive ion mode were identified between the two groups. These metabolites were correlated to multiple biological and metabolic processes, including various amino acid metabolism, membrane transport, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, ferroptosis, etc. three differential metabolites including glutathione, glutathione disulfide, arachidonic acid (peroxide free) were identified in the ferroptosis pathway. CIH was associated with a significant metabolic profiling change in mice liver. The metabolites in amino acid metabolism, membrane transport, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and ferroptosis played an important role in CIH-induced liver injury. These findings contribute to a better understanding of the mechanisms linking OSA and liver injury and help identify potential therapeutic targets.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
4.6
作者：
Xu H;Zheng X;Qian Y;Guan J;Yi H;Zou J;Wang Y;Meng L;Zhao A;Yin S;Jia W
通讯作者：
Jia W
影响因子：
3.3
作者：
Li, JG;Grigoryev, DN;Polotsky, VY
通讯作者：
Polotsky, VY
影响因子：
2.6
作者：
Chen, Li-Da;Zhang, Liang-Ji;Lin, Li
通讯作者：
Lin, Li
影响因子：
2.7
作者：
Savransky V;Reinke C;Jun J;Bevans-Fonti S;Nanayakkara A;Li J;Myers AC;Torbenson MS;Polotsky VY
通讯作者：
Polotsky VY