Metabolic analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography-mass spectrometry

Journal of Translational Medicine

Mingli Feng¹  Qin Cao¹  Xiaochun Wang¹  Tao Wang¹  Yuanye Jiang¹  Hui Lin¹  Xiaoyu Zhuang²  Cheng Hu²  Qiaoli Sun³  Jiaqi Zhang⁴ 

[1] Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, 200062, Shanghai, China;Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 200032, Shanghai, China;Shanghai TCM-Integrated Institute of Vascular Anomalies, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, 200082, Shanghai, China;

关键词: NAFLD;    Early diagnosis;    Metabolomics;    LC–MS/MS;    Biomarkers;   

DOI  :  10.1186/s12967-021-02820-7

来源: Springer

【 摘 要 】

BackgroundNonalcoholic fatty liver disease (NAFLD) is a common metabolic disease that affects 20–30% of individuals worldwide. Liver puncture remains the gold standard for the diagnosis of liver diseases despite limitations regarding invasive nature and sample variability. It is of great clinical significance to find noninvasive biomarkers to detect and predict NAFLD.ObjectiveThe aims of this study were to identify potential serum markers in individuals with early-stage NAFLD and to advance the mechanistic understanding of this disease using a high-throughput mass spectrometry-based untargeted metabolomics approach.MethodsOne hundred and twelve patients with early-stage NAFLD aged 18–55 were recruited according to the guidelines. The control group included 112 healthy participants. The demographic, anthropometric, clinical and laboratory data of all participants were systematically collected. Serum samples were obtained after an overnight fast. The comprehensive serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. The resultant data was processed by Compound Discover and SIMCA-P software to validate the potential biomarkers. Significantly altered metabolites were evaluated by variable importance in projection value (VIP > 1) and ANOVA (p < 0.01). Pathway analysis was performed using MetaboAnalyst 4.0.ResultsThe liver function test of early NAFLD patients showed no statistical differences to control group (p > 0.05). However, obvious differences in blood lipids were observed between subjects with NAFLD and controls (p < 0.001). In total, 55 metabolites showed significant changes in experimental group were identified. The area under curve (AUC) values deduced by receiver operating curve (ROC) analysis indicated that these newly identified biomarkers have high predictability and reliability. Of these, 15 metabolites with AUC greater than 0.9 were of great diagnostic value in early NAFLD patients.ConclusionIn this study, a total of 15 serum metabolites were found to strongly associate with early NAFLD. These biomarkers may have great clinical significance in the early diagnosis of NAFLD, as well as to follow response to therapeutic interventions.

【 授权许可】

CC BY