Department of Materials Research and Technology, Luxembourg Institute of Science and Technology, Belvaux 4422, Luxembourg.
Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette 4365, Luxembourg.
Anal Chem. 2023 Apr 25;95(16):6568-6576. doi: 10.1021/acs.analchem.2c05470. Epub 2023 Apr 7.
Perfluorooctanoic acid (PFOA) is a synthetic perfluorinated chemical classified as a persistent organic pollutant. PFOA has been linked to many toxic effects, including liver injury. Many studies report that PFOA exposure alters serum and hepatic lipid metabolism. However, lipidomic pathways altered by PFOA exposure are largely unknown and only a few lipid classes, mostly triacylglycerol (TG), are usually considered in lipid analysis. Here, we performed a global lipidomic analysis on the liver of PFOA-exposed (high-dose and short-duration) and control mice by combining three mass spectrometry (MS) techniques: liquid chromatography with tandem mass spectrometry (LC-MS/MS), matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). Among all hepatic lipids identified by LC-MS/MS analysis, more than 350 were statistically impacted (increased or decreased levels) after PFOA exposure, as confirmed by multi-variate data analysis. The levels of many lipid species from different lipid classes, most notably phosphatidylethanolamine (PE), phosphatidylcholine (PC), and TG, were significantly altered. Subsequent lipidomic analysis highlights the pathways significantly impacted by PFOA exposure, with the glycerophospholipid metabolism being the most impacted, and the changes in the lipidome network, which connects all the lipid species together. MALDI-MSI displays the heterogeneous distribution of the affected lipids and PFOA, revealing different areas of lipid expression linked to PFOA localization. TOF-SIMS localizes PFOA at the cellular level, supporting MALDI-MSI results. This multi-modal MS analysis unveils the lipidomic impact of PFOA in the mouse liver after high-dose and short-term exposure and opens new opportunities in toxicology.
全氟辛酸（PFOA）是一种合成的全氟化化学物质，被归类为持久性有机污染物。PFOA 与许多毒性作用有关，包括肝损伤。许多研究报告称，PFOA 暴露会改变血清和肝脏脂质代谢。然而，PFOA 暴露改变的脂质组学途径在很大程度上是未知的，并且在脂质分析中通常只考虑少数脂质类，主要是三酰基甘油（TG）。在这里，我们通过结合三种质谱（MS）技术：液相色谱与串联质谱（LC-MS/MS）、基质辅助激光解吸电离质谱成像（MALDI-MSI）和飞行时间二次离子质谱（TOF-SIMS），对 PFOA 暴露（高剂量和短时间）和对照小鼠的肝脏进行了全面的脂质组学分析。在通过 LC-MS/MS 分析鉴定的所有肝脏脂质中，超过 350 种脂质的水平在 PFOA 暴露后受到统计学影响（水平升高或降低），这一点得到了多变量数据分析的证实。来自不同脂质类别的许多脂质物种的水平发生了显著变化，尤其是磷脂酰乙醇胺（PE）、磷脂酰胆碱（PC）和 TG。随后的脂质组学分析突出了受 PFOA 暴露影响的途径，其中甘油磷脂代谢受影响最大，以及脂质组网络的变化，该网络将所有脂质物种连接在一起。MALDI-MSI 显示受影响脂质和 PFOA 的异质分布，揭示了与 PFOA 定位相关的不同脂质表达区域。TOF-SIMS 在细胞水平上定位 PFOA，支持 MALDI-MSI 结果。这种多模态 MS 分析揭示了 PFOA 在小鼠肝脏中的脂质组学影响，这种影响是在高剂量和短时间暴露后产生的，为毒理学开辟了新的机会。
