Hepatic nontargeted lipidomics study for mechanism of Shaqi concen-trated pills attenuating high-fat diet-induced metabolic dysfunction-asso-ciated fatty liver disease in mice
10.3969/j.issn.1000-4718.2025.08.006
- VernacularTitle:通过肝脏非靶向脂质组学探讨沙芪浓缩丸缓解高脂饮食诱导的小鼠代谢功能障碍相关脂肪性肝病的机制
- Author:
Shuyin BAO
1
;
Xuan WANG
;
Pengju BAI
;
Qiong WU
;
Qianqian MA
Author Information
1. 内蒙古民族学公共卫生学院,内蒙古 通辽 028000;内蒙古民族大学糖脂代谢紊乱干预策略与新药研究创新团队,内蒙古 通辽 028000
- Publication Type:Journal Article
- Keywords:
metabolic dysfunction-associated fatty liver disease;
Shaqi concentrated pills;
lipidomics
- From:
Chinese Journal of Pathophysiology
2025;41(8):1504-1513
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aimed to investigate the differences in hepatic lipid metabolites in ICR mice in-duced by a high-fat diet and treated with Shaqi concentrated pills(SQ).METHODS:Thirty 8-week-old SPF-grade ICR mice were randomly assigned to five groups:the normal(CON,n=6)group,the high-fat diet model(HFD,n=6)group,the low-dose SQ administration(SQL,n=6)group,the high-dose SQ administration(SQH,n=6)group,and the liver-protecting tablets positive control(PLT,n=6)group.The HFD group was fed a diet consisting of 60%fat for 8 weeks to es-tablish a metabolic-dysfunction-associated fatty liver disease model.Upon successful model establishment,the SQL group received a daily gavage of 395 mg/kg for 4 weeks,while the SQH group received 790 mg·kg-1·d-1.The PLT group was ad-ministered liver-protecting tablets at a dosage of 0.655 g/kg via gavage.Body weight and food intake were monitored week-ly.Liver indices,including Lee's index,triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT),and aspartate transaminase(AST)levels,were measured in each group.Hematoxylin-eosin(HE)staining and oil red O staining were performed to assess the extent of pathological damage in liver tissues.Western blot analysis was conducted to evaluate the protein expres-sion levels of choline/ethanolamine phosphotransferase-1(CEPT1),adipose triglyceride lipase(ATGL),and diacylglycerol acyltransferase(DGAT)in the liver.A non-targeted lipidomic analysis using LC-MS was employed to detect changes in hepatic lipid content,and multivariate statistical analyses(principal component analysis and orthogonal partial least squares discriminant analysis)were utilized to compare lipid metabolic profiles among the groups and identify differential lipid metabolites.RESULTS:Compared to the CON group,mice in the HFD group exhibited significantly increased body weight,blood glucose levels,serum TG,TC,LDL-C,ALT,and AST levels,accompanied by a marked decrease in HDL-C levels.HE and oil red O staining results revealed significant lipid droplet accumulation in the liver tissues of HFD mice.In contrast,mice in the SQL and SQH groups showed significant reductions in body weight,blood glucose,serum TG,TC,LDL-C,ALT,and AST levels,along with increased HDL-C levels and less lipid accumulation in liver tissues compared to the HFD group.Staining of liver sections confirmed that SQ treatment mitigated the abnormal accumulation of lipid droplets.Lipidomic analysis indicated that SQ treatment normalized 25 aberrantly expressed lipid metabolites to lev-els comparable to the CON group and identified nine representative differential lipid metabolites.Western blot results dem-onstrated that SQ treatment reduced the protein expression levels of ATGL and DGAT while increasing the expression of CEPT1.CONCLUSION:Treatment with SQ can alleviate metabolic dysfunction-associated fatty liver disease(MAFLD)by modulating triglyceride metabolism,phosphatidylcholine metabolism,and dimethylphosphatidylethanolamine lipid me-tabolism,thereby altering the hepatic lipid profile in MAFLD mice.
