Abstract

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent with identifiable risk factors including obesity, hyperlipidemia and diabetes. A lipidomic approach was taken to quantify the major lipid classes in human serum. Comprehensive characterization of serum lipids determined by ultraperformance liquid chromatography (UPLC)-mass spectrometry (MS) was performed in NAFLD patients and healthy controls. Nine lipid subgroups including lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), cholesterol ester (ChE), diacylglyceride (DG), triglyceride (TG), sphingomyelin (SM), and ceramide (Cer) were determined in the positive ionization mode. The current study further corroborates existing evidence that increased TG and DG accumulation is the hallmark. The results showed that compared with healthy controls, the abundance of PC in the sera of NAFLD patients decreased, and the phosphatidylethanolamine (PE) level increased, resulting in a reduced PC/PE ratio in NAFLD patients. In NAFLD samples, Cer(18:0/16:0), Cer(18:1/24:0), and Cer(18:1/24:1) were present at significantly higher levels than in controls, while the Cer(18:0/14:0) and Cer(18:0/20:0) levels were lower. In addition, the determination of sphingolipids showed that the abundances of long-chain ceramides were significantly increased in NAFLD patients. These results demonstrate the identification of NAFLD using UPLC-MS lipidomics and provide insights into changes in lipids associated with this disease.

摘要

非酒精性脂肪性肝病 (NAFLD) 非常普遍，具有可识别的危险因素，包括肥胖、高脂血症和糖尿病。采用脂质组学方法来量化人血清中的主要脂质类别。在 NAFLD 患者和健康对照组中进行了通过超高效液相色谱 (UPLC)-质谱 (MS) 测定的血清脂质的综合表征。九个脂质亚群包括溶血磷脂酰胆碱 (LPC)、溶血磷脂酰乙醇胺 (LPE)、磷脂酰胆碱 (PC)、磷脂酰乙醇胺 (PE)、胆固醇酯 (ChE)、甘油二酯 (DG)、甘油三酯 (TG)、鞘磷脂 (SM) 和神经酰胺 (Cer)在正离子模式下测定。目前的研究进一步证实了现有证据表明增加的 TG 和 DG 积累是标志。结果显示，与健康对照组相比，NAFLD患者血清中PC丰度降低，磷脂酰乙醇胺（PE）水平升高，导致NAFLD患者PC/PE比值降低。在 NAFLD 样本中，Cer(18:0/16:0)、Cer(18:1/24:0) 和 Cer(18:1/24:1) 的含量显着高于对照组，而 Cer (18:0/14:0) 和 Cer(18:0/20:0) 水平较低。此外，鞘脂的测定表明，NAFLD 患者中长链神经酰胺的丰度显着增加。这些结果证明了使用 UPLC-MS 脂质组学鉴定 NAFLD 并提供与该疾病相关的脂质变化的见解。导致 NAFLD 患者的 PC/PE 比率降低。在 NAFLD 样本中，Cer(18:0/16:0)、Cer(18:1/24:0) 和 Cer(18:1/24:1) 的含量显着高于对照组，而 Cer (18:0/14:0) 和 Cer(18:0/20:0) 水平较低。此外，鞘脂的测定表明，NAFLD 患者中长链神经酰胺的丰度显着增加。这些结果证明了使用 UPLC-MS 脂质组学鉴定 NAFLD 并提供与该疾病相关的脂质变化的见解。导致 NAFLD 患者的 PC/PE 比率降低。在 NAFLD 样本中，Cer(18:0/16:0)、Cer(18:1/24:0) 和 Cer(18:1/24:1) 的含量显着高于对照组，而 Cer (18:0/14:0) 和 Cer(18:0/20:0) 水平较低。此外，鞘脂的测定表明，NAFLD 患者中长链神经酰胺的丰度显着增加。这些结果证明了使用 UPLC-MS 脂质组学鉴定 NAFLD 并提供与该疾病相关的脂质变化的见解。鞘脂的测定表明，NAFLD 患者中长链神经酰胺的丰度显着增加。这些结果证明了使用 UPLC-MS 脂质组学鉴定 NAFLD 并提供与该疾病相关的脂质变化的见解。鞘脂的测定表明，NAFLD 患者中长链神经酰胺的丰度显着增加。这些结果证明了使用 UPLC-MS 脂质组学鉴定 NAFLD 并提供与该疾病相关的脂质变化的见解。