Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines

Nonalcoholic steatohepatitis(NASH)is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder.Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH,while the other lipids associated with the NASH pathogenesis remained unexplored.The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids.Herein,multi-omics techniques based on LC—Q-TOF/MS,LC—MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment.A methionine and choline deficient(MCD)diet-induced mouse model of NASH was then constructed,and Schisandra lignans extract(SLE)was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14.Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines(PEs),and SLE could significantly reduce the accumulation of intrahepatic PEs.Notably,exogenous PE(18:0/18:1)was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis.Supplementing PE(18:0/18:1)also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors,while PE synthase inhibitor exerted a prominent hepatoprotective role.The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

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

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.