Non-alcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis. However, NAFLD's global impact on the liver lipidome is poorly understood. Using high-resolution shotgun mass spectrometry, we quantified the molar abundance of 316 species from 22 major lipid classes in liver biopsies of 365 patients, including non-steatotic patients with normal or excessive weight, patients diagnosed with NAFL (non-alcoholic fatty liver) or NASH (non-alcoholic steatohepatitis), and patients bearing common mutations of NAFLD-related protein factors. We confirmed the progressive accumulation of di- and tri- acylglycerols and cholesteryl esters in the liver of NAFL and NASH patients, while the bulk composition of glycerophospho- and sphingolipids remained unchanged. Further stratification by biclustering analysis identified sphingomyelin species comprising n24:2 fatty acid moieties as membrane lipid markers of NAFLD. Normalized relative abundance of sphingomyelins SM 43:3;2 and SM 43:1;2 containing n24:2 and n24:0 fatty acid moieties, respectively, showed opposite trends during NAFLD progression and distinguished NAFL and NASH lipidomes from the lipidome of non-steatoic livers. Together with several glycerophospholipids containing a C22:6 fatty acid moiety, these lipids serve as markers of early and advanced stages of NAFL.

中文翻译：

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非酒精性脂肪肝疾病肝脏脂质组学分层。

非酒精性脂肪性肝病 (NAFLD) 是一种常见的代谢功能障碍，可导致肝脂肪变性。然而，人们对 NAFLD 对肝脏脂质组的全球影响知之甚少。使用高分辨率鸟枪质谱法，我们量化了 365 名患者肝活检中 22 个主要脂质类别中 316 种物质的摩尔丰度，包括体重正常或超重的非脂肪变性患者、诊断为 NAFL（非酒精性脂肪肝）的患者或 NASH（非酒精性脂肪性肝炎），以及携带 NAFLD 相关蛋白因子常见突变的患者。我们证实了 NAFL 和 NASH 患者肝脏中甘油二酯、甘油三酯和胆固醇酯的逐渐积累，而甘油磷酸酯和鞘脂的大部分组成保持不变。通过双聚类分析进一步分层确定了包含 n24:2 脂肪酸部分的鞘磷脂物种作为 NAFLD 的膜脂标记物。分别含有 n24:2 和 n24:0 脂肪酸部分的鞘磷脂 SM 43:3;2 和 SM 43:1;2 的标准化相对丰度在 NAFLD 进展过程中显示出相反的趋势，并将 NAFL 和 NASH 脂质组与非脂肪肝。与几种含有 C22:6 脂肪酸部分的甘油磷脂一起，这些脂质可作为 NAFL 早期和晚期的标志物。在 NAFLD 进展过程中显示出相反的趋势，并将 NAFL 和 NASH 脂质组与非脂肪肝的脂质组区分开来。与几种含有 C22:6 脂肪酸部分的甘油磷脂一起，这些脂质可作为 NAFL 早期和晚期的标志物。在 NAFLD 进展过程中显示出相反的趋势，并将 NAFL 和 NASH 脂质组与非脂肪肝的脂质组区分开来。与几种含有 C22:6 脂肪酸部分的甘油磷脂一起，这些脂质可作为 NAFL 早期和晚期的标志物。