Abstract
Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of scoparone on lipid metabolism in hepatocytes. The most striking finding was that scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics.
Highlights
Lipids play an outstanding role in diverse biological functions, including structural, energetic, and regulatory functions[1]
Lipids were extracted from exposed cells and analyzed by Ultra Performance Liquid Chromatography (UPLC)-Time of flight (TOF)-MS in full scan mode, together with imaging supported by TransOmics tool
Typical base peak ion (BPI) chromatograms of the cellular samples on UPLC-MS are shown in Fig. 1A and Fig. S2A
Summary
Lipids play an outstanding role in diverse biological functions, including structural, energetic, and regulatory functions[1]. ALD is a multifaceted disease that is characterized by a broad spectrum of liver injury[6]. It increases the economic burden on society[7]. Greater efforts have been spent on the understanding of the mechanism, the cellular molecular lipid details for the metabolic functions in the ethanol-injured hepatic injury are not yet completely understood. Scoparone (Fig. S1), a plant-derived coumarin, has antioxidative and hepatoprotective effects[11]. It was absorbed into the blood circulation within a few minutes, and the time to peak was at ~1 h after oral administration[12]. The novel strategy presented here has the potential to open new detailed insights into the lipid metabolism that may lead to a better understanding of physiological mechanisms and metabolic perturbations, and has the potential to impact on drug discovery and development
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