基于HPLC-MS脂质组学研究棕榈酸 对人正常肝细胞脂质代谢的影响

对棕榈酸（PA）处理的人源肝细胞中的脂质进行脂质组学分析，探讨PA对肝细胞脂质代谢的影响。采用基于HPLC-MS的脂质组学技术，识别和量化PA处理人正常肝细胞后改变的内源性脂质代谢产物，并利用流式细胞仪检测细胞周期变化。结果表明，通过脂质组学分析共检测到1 000多种脂质代谢物，又可细分为22种质类别，根据正交偏最小二乘判别分析（OPLS-DA）显示有628种脂质代谢物含量存在显著差异。其中PA处理组中溶血磷脂酰胆碱（LPC）、磷脂酰肌醇（PI）、神经酰胺（Cer）、己糖神经酰胺（Hex1Cer）、鞘氨醇（SPH）、甘油二酯（DG）、甘油三酯（TG）、酰基肉碱（AcCa）和N-酰基乙醇胺（AEA）含量显著升高，鞘磷脂（SM）、二己糖神经酰胺（Hex2Cer）和胆固醇酯（ChE）含量显著下降。与对照组相比，PA处理组G0/G1期细胞比例下降，S期和G2/M期细胞比例上升，即细胞周期发生阻滞。综上，PA显著改变了肝细胞的脂质代谢谱，诱导细胞G2/M期阻滞。

Effect of palmitic acid on lipid metabolism of human normal liver cells based on HPLC-MS lipidomics

Lipidomics analysis of lipids in palmitic acid (PA)-treated human-derived hepatocytes was performed to explore the effect of PA on hepatocyte lipid metabolism. HPLC-MS-based lipidomics technique was used to identify and quantify the endogenous lipid metabolites altered after PA administration, and cell cycle analysis was performed by flow cytometer. The results showed that 1 000 lipid metabolites subdivided in to 22 lipid classes were identified by lipidomics analysis and 628 lipid species levels showed significant difference according to the orthogonal partial least squares discriminant analysis (OPLS-DA). Among them, lysophosphatidylcholine (LPC), phosphatidylinositol (PI), ceramide (Cer), hexose1ceramide (Hex1Cer), sphingosine (SPH), diglyceride (DG), triglyceride (TG), acetylcarnitine (AcCa) and N-acyl ethanolamine (AEA) were significantly higher in the PA-treated group, and sphingomyelin (SM), hexose2ceramide (Hex2Cer) and cholesteryl ester (ChE) significantly decreased. Compared with the control group, the proportion of cells in G0/G1 phase decreased and those in S and G2/M phase increased in the PA-treated group.In conclusion, PA significantly altered the lipid metabolic profile of hepatocytes and induced cellular G2/M phase arrest.