The role of phosphatidylcholine 34:1 in the occurrence,development and treatment of ulcerative colitis  

作　　者：Tengjie Yu Zhihao Zhou Shijia Liu Changjian Li Zhi-Wei Zhang Yong Zhang Wei Jin Keanqi Liu Shuying Mao Lei Zhu Lin Xie Guangji Wang Yan Liang 

机构地区：[1]Key Lab of Drug Metabolism&Pharmacokinetics,State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China [2]Affliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210000,China [3]College of Chemical&Pharmaceutical Engineering,Hebei University of Science&Technology,Shijiazhuang 050018,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第3期1231-1245,共15页药学学报（英文版）

基　　金：supported by the Jiangsu Natural Science Funds(BK20211224,China);the Natural Science Foundation of Hebei Province(Nos.H2021302001,H2020208022,H2020208025,C2021418001,H2021208006,China);the CAMS Innovation Fund for Medical Sciences(2021-I2M-5-011,China).

摘　　要：Lipid homeostasis is considered to be related to intestinal metabolic balance,while its role in the pathogenesis and treatment of ulcerative colitis(UC)remains largely unexplored.The present study aimed to identify the target lipids related to the occurrence,development and treatment of UC by comparing the lipidomics of UC patients,mice and colonic organoids with the corresponding healthy controls.Here,multi-dimensional lipidomics based on LC–QTOF/MS,LC–MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles.The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis,in which triglycerides and phosphatidylcholines were significantly reduced.Notably,phosphatidylcholine 34:1(PC34:1)was characterized by high abundance and closely correlation with UC disease.Our results also revealed that down-regulation of PC synthase PCYT1 α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1,and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate,thus exerting an anti-UC effect.Collectively,our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals,but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.

关 键 词：Ulcerative colitis LIPIDOMICS PC34:1 METABONOMICS FUMARATE 

分 类 号：R574.62[医药卫生—消化系统]