尽管酒精性肝病的患病率很高，但其鉴定和表征仍然很差，特别是在早期阶段，如酒精性脂肪肝病和酒精性脂肪肝炎等。后者暗示着诊断困难、少有治疗选择和作用机制不明确。为了阐明代谢变化和确定受影响的生化途径，通过在HepaRG细胞中暴露于乙醇（IC10，368毫摩尔）和肿瘤坏死因子α（TNF-α，50 ng/mL）24小时来体外模拟了酒精性脂肪肝炎。将这种联合暴露与仅暴露于乙醇及未经暴露的细胞进行比较。使用四种不同的代谢组学平台，结合液相色谱法、高分辨率质谱法和漂移管离子迁移技术，阐明细胞内和细胞外的代谢变化。一些关键发现包括TNF-α在调节肝三酰甘油水平上的影响和调节肝磷脂酰乙醇胺和磷脂酰胆碱水平的下降。S-腺苷甲硫氨酸显示出在酒精性脂肪肝炎的进展中发挥核心作用。此外，氢氧基脂肪酸（FAHFA）酯类含有的三酰甘油在人肝细胞中首次被检测到，并且它们的变化在酒精性脂肪肝炎的进展中显示出潜在的重要作用。氧乙基化磷酰胆碱被确定为乙醇暴露的潜在新生物标志物。©2023年。作者（们）独家授权于Springer-Verlag GmbH Germany，Springer Nature公司的一部分。

Despite the high prevalence of alcoholic liver disease, its identification and characterization remain poor, especially in early stages such as alcoholic fatty liver disease and alcoholic steatohepatitis. This latter implies diagnostic difficulties, few therapeutic options and unclear mechanisms of action. To elucidate the metabolic alterations and pinpoint affected biochemical pathways, alcoholic steatohepatitis was simulated in vitro by exposing HepaRG cells to ethanol (IC10, 368 mM) and tumor necrosis factor alpha (TNF-α, 50 ng/mL) for 24 h. This combined exposure was compared to solely ethanol-exposed as well as -nonexposed cells. Four different metabolomics platforms were used combining liquid chromatography, high-resolution mass spectrometry and drift tube ion mobility to elucidate both intracellular and extracellular metabolic alterations. Some of the key findings include the influence of TNF-α in the upregulation of hepatic triglycerides and the downregulation of hepatic phosphatidylethanolamines and phosphatidylcholines. S-Adenosylmethionine showed to play a central role in the progression of alcoholic steatohepatitis. In addition, fatty acyl esters of hydroxy fatty acid (FAHFA)-containing triglycerides were detected for the first time in human hepatocytes and their alterations showed a potentially important role during the progression of alcoholic steatohepatitis. Ethoxylated phosphorylcholine was identified as a potential new biomarker of ethanol exposure.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.