Integration of Metabolomics, Lipidomics, and Proteomics Reveals the Metabolic Characterization of Nonalcoholic Steatohepatitis.
Integration of Metabolomics, Lipidomics, and Proteomics Reveals the Metabolic Characterization of Nonalcoholic Steatohepatitis.
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DOI：
10.1021/acs.jproteome.3c00009
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发表时间：
2023-07
影响因子：
4.4
通讯作者：
Ji Zhang;Yiqin Yang;Zipeng Wang;Xiaofen Zhang;Yingfan Zhang;Jiashuo Lin;Yue Du;Su Wang;Dandan Si;J. Bao;Xin Tian
中科院分区：
文献类型：
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作者：
Ji Zhang;Yiqin Yang;Zipeng Wang;Xiaofen Zhang;Yingfan Zhang;Jiashuo Lin;Yue Du;Su Wang;Dandan Si;J. Bao;Xin Tian
代谢功能障碍与非酒精性脂肪性肝炎（NASH）的发展相关。然而，研究NASH患者代谢变化的组学研究有限。在这项研究中，进行了血浆中的代谢组学和脂质组学以及肝脏中的蛋白质组学，以表征NASH患者的代谢谱。此外，NASH患者胆汁酸（BA）的积累促使我们研究消胆胺对NASH的保护作用。NASH患者肝脏中参与FA转运和脂滴的必需蛋白表达显著升高。此外，我们观察到NASH患者存在明显的脂质组学重构。我们还报告了一项新的发现，表明NASH患者中负责糖酵解的关键蛋白质的表达和糖酵解输出（糖酵解酸）水平增加。此外，在NASH患者中观察到支链氨基酸、芳香族氨基酸、嘌呤和BA的积累。类似地，在NASH小鼠模型中也观察到显著的代谢紊乱。消胆胺不仅能显著减轻肝脂肪变性和纤维化，而且能逆转NASH诱导的BA和类固醇激素的蓄积。总之，NASH患者的特征在于FA摄取、脂滴形成、糖酵解以及BA和其他代谢物的积累的扰动。
Metabolic dysfunction is associated with nonalcoholic steatohepatitis (NASH) development. However, omics studies investigating metabolic changes in NASH patients are limited. In this study, metabolomics and lipidomics in plasma, as well as proteomics in the liver, were performed to characterize the metabolic profiles of NASH patients. Moreover, the accumulation of bile acids (BAs) in NASH patients prompted us to investigate the protective effect of cholestyramine on NASH. The liver expression of essential proteins involved in FA transport and lipid droplets was significantly elevated in patients with NASH. Furthermore, we observed a distinct lipidomic remodeling in patients with NASH. We also report a novel finding suggesting an increase in the expression of critical proteins responsible for glycolysis and the level of glycolytic output (pyruvic acid) in patients with NASH. Furthermore, the accumulation of branched chain amino acids, aromatic amino acids, purines, and BAs was observed in NASH patients. Similarly, a dramatic metabolic disorder was also observed in a NASH mouse model. Cholestyramine not only significantly alleviated liver steatosis and fibrosis but also reversed NASH-induced accumulation of BAs and steroid hormones. In conclusion, NASH patients were characterized by perturbations in FA uptake, lipid droplet formation, glycolysis, and accumulation of BAs and other metabolites.