Literature DB >> 34939051

A pilot study optimizing metabolomic and lipidomic acquisition in serum for biomarker discovery in nonalcoholic fatty liver disease.

Dandan He1, Yang Su2, Duanyue Meng2, Xinmiao Wang3, Jun Wang4, Hui Ye3.   

Abstract

BACKGROUND: The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) has stimulated work to identify biomarkers and develop effective treatments. Metabolomics is an emerging tool that has been widely applied to discover biomarkers and simultaneously uncover pathological mechanisms. Here, we aim to optimize metabolomic acquisition with the goal of obtaining a systemic metabolic profile to unravel the potential link between dysregulated metabolism and NAFLD.
METHODS: We analyzed serum samples collected from healthy subjects (n = 8) and NAFLD patients (n = 8) via an integrative analytical workflow using two orthogonal separation modes with T3 and amide columns and two ionization polarity modes on a UPLC-ESI-Q/TOF. Data dependent acquisition was employed for data acquisition. Differentially expressed metabolites and lipids were identified by comparing the collected metabolic and lipidomic profiles between the healthy subjects and NAFLD patients.
RESULTS: The integrative LC-MS/MS analytical workflow employed here features an improved coverage of metabolites and lipids, which leads to the identification of 20 potential biomarkers of NAFLD, including lipids, acylcarnitines, and organic acids.
CONCLUSIONS: This pilot study has identified potential biomarkers for NAFLD and revealed corresponding dysregulated metabolic pathways related to NAFLD's occurrence and progression, establishing a molecular basis for NAFLD diagnosis and therapeutic intervention. ©2021THEAUTHORS.PublishingservicesbyELSEVIERB.V.

Entities:  

Keywords:  ACN, acetonitrile; Acylcarnitines; DGs, diacylglycerols; EICs, extracted ion chromatograms; ESI− and ESI+, ionization polarity modes; FA, Formic acid; FC, fold change; HCC, hepatocellular carcinoma; HFD, high-fat diet; HILIC, hydrophilic interaction chromatography; LE, Leucine enkephalin; LPC, lysophosphatidylcholine; Lipids; MCD, methionine-choline-deficient; MGs, monoacylglycerols; MS, mass spectrometry; Metabolic biomarkers; Metabolomics; NAFLD; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; OPLS-DA, orthogonal partial least square discriminant analysis; PCs, phosphorylcholines; PEs, phosphatidylethanolamines; PKC∊, protein kinase C∊; ROC, receiver operating characteristic; RPLC, reversed-phase liquid chromatography; T3-neg, T3 column-based reverse phase separation plus the negative ion mode; T3-pos, T3 column-based reverse phase separation plus the positive ion mode; TIC, total ion chromatogram; VIP, variable importance; amide-neg, amide column-based HILIC separation plus the negative ion mode; amide-pos, amide column-based HILIC separation plus the positive ion mode

Year:  2021        PMID: 34939051      PMCID: PMC8662338          DOI: 10.1016/j.jmsacl.2021.10.001

Source DB:  PubMed          Journal:  J Mass Spectrom Adv Clin Lab        ISSN: 2667-145X


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