High-throughput metabolomics screen coupled with multivariate statistical analysis identifies therapeutic targets in alcoholic liver disease rats using liquid chromatography-mass spectrometry.


National Chinmedomics Research Center, Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, China. Electronic address: [Email]


Identification of metabolic alterations is useful for elucidating the pathophysiology and mass spectrometry-aided metabolomic, which provides small molecule metabolites to understand underlying mechanisms of complex diseases. In this work, we developed a novel liquid chromatography coupled with tandem mass spectrometry-based metabolomics screen coupled with multivariate statistical analysis workflow to obtaining the metabolite annotation, visualization and rapid characterization of small molecular metabolites, then revealed the altered metabolic pathway in a rat model of alcohol-induced liver damage rats as case study. The ions were detected in both positive and negative mode, and the key biomarkers were selected through multivariate statistical screening analysis. We employed the enhanced mass spectrometry coverage method to comprehensive analysis of the metabolite data. Importantly, we further find these small molecule metabolites were associated with multiple metabolic pathways. The elucidation of these altered metabolic pathways should help identify new and specific therapeutic targets. In addition, this metabolomics workflow coupled to LC-MS/MS has been successfully applied to the identification of small molecule metabolites in this complex disease. We strongly believe that metabolomics studies will benefit from incorporating liquid chromatography coupled with tandem mass spectrometry strategies.

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