Study on the Mechanism of Quzhuo Tongbi Formula Relieving Bile Acid Metabolism Disorder Induced by High Fat Diet in Mice Based on Serum Metabolomics
10.16466/j.issn1005-5509.2024.10.001
- VernacularTitle:基于血清代谢组学研究祛浊通痹方改善高脂饮食诱导的肥胖小鼠胆汁酸代谢紊乱
- Author:
Xinyi XU
1
;
Yan ZHENG
;
Zhenzhen FANG
Author Information
1. 浙江中医药大学附属第三医院 杭州 310005;浙江中医药大学药学院
- Keywords:
hyperlipidemia;
serum metabolomics;
Quzhuo Tongbi Formula;
biomarkers;
FXR-SHP;
bile acid metabolism;
ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry;
target validation
- From:
Journal of Zhejiang Chinese Medical University
2024;48(10):1191-1198
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To study the mechanism of Quzhuo Tongbi Formula(QZTB)in improving bile acid metabolism disorder induced by high fat diet(HFD)in mice using serum metabolomics.[Methods]Male C57BL/6J mice were randomly divided into blank,HFD model and QZTB groups.Serum metabolomic analysis was performed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS)technique to screen potential biomarkers.The key targets on the enriched pathway were verified using Real-time quantitative polymerase chain reaction(RT-qPCR)method.[Results]A total of 103 potential biomarkers were screened using serum metabolomics analysis,mainly enriched in bile acid bioanabolic pathway.QZTB treatment could significantly improve the bile acid metabolism disorder induced by HFD in mice.RT-qPCR results showed that compared with blank group,the expression levels of cholesterol 7-alpha hydroxylase(CYP7A1)and cytochrome P450 family 8 subfamily B member 1(CYP8B1)in liver tissue of HFD model group were inhibited(P<0.01),and the expressions of farnitol X receptor(FXR)and small heterodimeric partner(SHP)also decreased(P<0.01,P<0.01,P<0.001,P<0.01).After QZTB treatment,the levels of key enzymes such as CYP7A1 and CYP8B1 on the classical pathway increased(P<0.01,P<0.05).FXR-SHP pathway was activated(P<0.05),thereby sterol regulatory element binding protein-1C(SREBP-1C)and fatty acid synthase(FAS)were inhibited(P<0.01,P<0.001).[Conclusion]QZTB could improve bile acid metabolism disorder induced by HFD in obese mice,which be attributed to increasing the activity of key enzymes in the classical bile acid synthase,promoting the synthesis of primary bile acid,activating FXR-SHP pathway,and further regulating bile acid biosynthesis metabolism.
