Chen Hua, Chen Lin, Liu Dan, Chen Dan-Qian, Vaziri Nosratola D, Yu Xiao-Yong, Zhang Li, Su Wei, Bai Xu, Zhao Ying-Yong
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University , No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
Division of Nephrology and Hypertension, School of Medicine, University of California Irvine , MedSci 1 C352, Irvine, California 92897, United States.
J Proteome Res. 2017 Apr 7;16(4):1566-1578. doi: 10.1021/acs.jproteome.6b00956. Epub 2017 Mar 27.
Chronic kidney disease (CKD) results in significant dyslipidemia and profound changes in lipid and lipoprotein metabolism. The associated dyslipidemia, in turn, contributes to progression of CKD and its cardiovascular complications. To gain an in-depth insight into the disorders of lipid metabolism in advanced CKD, we applied UPLC-HDMS-based lipidomics to measure serum lipid metabolites in 180 patients with advanced CKD and 120 age-matched healthy controls. We found significant increases in the levels of total free fatty acids, glycerolipids, and glycerophospholipids in patients with CKD. The levels of free fatty acids, glycerolipids, and glycerophospholipids directly correlated with the level of serum triglyceride and inversely correlated with the levels of total cholesterol and eGFR. A total of 126 lipid species were identified from positive and negative ion modes. Out of 126, 113 identified lipid species were significantly altered in patients with CKD based on the adjusted FDR method. These results pointed to profound disturbance of fatty acid and triglyceride metabolisms in patients with CKD. Logistic regression analysis showed strong correlations between serum methyl hexadecanoic acid, LPC(24:1), 3-oxooctadecanoic acid, and PC(20:2/24:1) levels with eGFR and serum creatinine levels (R > 0.8758). In conclusion, application of UPLC-HDMS-based lipidomic technique revealed profound changes in lipid metabolites in patients with CKD. The observed increases in serum total fatty acids, glycerolipids, and glycerophospholipids levels directly correlated with increased serum triglyceride level and inversely correlated with the eGFR and triglyceride levels.
慢性肾脏病（CKD）会导致显著的血脂异常以及脂质和脂蛋白代谢的深刻变化。而相关的血脂异常反过来又会促进CKD的进展及其心血管并发症。为了深入了解晚期CKD患者脂质代谢紊乱情况，我们应用基于超高效液相色谱-高分辨质谱联用（UPLC-HDMS）的脂质组学技术来检测180例晚期CKD患者和120例年龄匹配的健康对照者的血清脂质代谢产物。我们发现CKD患者的总游离脂肪酸、甘油酯和甘油磷脂水平显著升高。游离脂肪酸、甘油酯和甘油磷脂水平与血清甘油三酯水平直接相关，与总胆固醇水平和估算肾小球滤过率（eGFR）呈负相关。从正离子和负离子模式中共鉴定出126种脂质种类。基于校正后的错误发现率（FDR）方法，在这126种脂质种类中，有113种在CKD患者中发生了显著变化。这些结果表明CKD患者的脂肪酸和甘油三酯代谢存在严重紊乱。逻辑回归分析显示血清甲基十六烷酸、溶血磷脂酰胆碱（LPC，24:1）、3-氧代十八烷酸和磷脂酰胆碱（PC，20:2/24:1）水平与eGFR和血清肌酐水平之间存在强相关性（R>0.8758）。总之，基于UPLC-HDMS的脂质组学技术应用揭示了CKD患者脂质代谢产物的深刻变化。观察到的血清总脂肪酸、甘油酯和甘油磷脂水平升高与血清甘油三酯水平升高直接相关，与eGFR和总胆固醇水平呈负相关。
