Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease.
Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease.
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DOI：
10.3748/wjg.v23.i15.2771
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发表时间：
2017-04-21
影响因子：
4.3
通讯作者：
Sun MY
中科院分区：
文献类型：
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作者：
Dong S;Zhan ZY;Cao HY;Wu C;Bian YQ;Li JY;Cheng GH;Liu P;Sun MY
目的寻找一组能够区分非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）的生物标志物，并探讨NAFLD发展为NASH的分子机制。生物标志物在NAFLD的各个阶段可能不同。从具有NAFLD和脂肪变性、肝功能正常的非糖尿病受试者（n = 33）、具有肝功能异常的NASH患者（n = 45）以及健康年龄和性别匹配的对照（n = 30）获得尿液和血液。对样品进行代谢组学分析以鉴定潜在的非侵入性生物标志物。尿代谢谱的差异进行了分析，采用液相色谱串联质谱与主成分分析和偏最小二乘判别分析。与NAFLD患者相比，NASH患者存在肝功能异常和高血脂水平。尿代谢组学发现这两组之间的31种代谢物存在差异，包括核酸和氨基酸的差异。基于重叠代谢物的途径分析表明，能量和氨基酸代谢途径以及戊糖磷酸途径与NAFLD和NASH的病理过程密切相关。这些发现表明，一组生物标志物可以区分NAFLD和NASH，并有助于确定从NAFLD发展为NASH过程中所涉及的分子机制。尿液生物标志物可用于诊断这些患者，并可用于评估对治疗干预的反应。
To identify a panel of biomarkers that can distinguish between non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and explore molecular mechanism involved in the process of developing NASH from NAFLD. Biomarkers may differ during stages of NAFLD. Urine and blood were obtained from non-diabetic subjects with NAFLD and steatosis, with normal liver function (n = 33), from patients with NASH, with abnormal liver function (n = 45), and from healthy age and sex-matched controls (n = 30). Samples were subjected to metabolomic analysis to identify potential non-invasive biomarkers. Differences in urinary metabolic profiles were analyzed using liquid chromatography tandem mass spectrometry with principal component analysis and partial least squares-discriminate analysis. Compared with NAFLD patients, patients with NASH had abnormal liver function and high serum lipid concentrations. Urinary metabonomics found differences in 31 metabolites between these two groups, including differences in nucleic acids and amino acids. Pathway analysis based on overlapping metabolites showed that pathways of energy and amino acid metabolism, as well as the pentose phosphate pathway, were closely associated with pathological processes in NAFLD and NASH. These findings suggested that a panel of biomarkers could distinguish between NAFLD and NASH, and could help to determine the molecular mechanism involved in the process of developing NASH from NAFLD. Urinary biomarkers may be diagnostic in these patients and could be used to assess responses to therapeutic interventions.