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Metabolomic Study of High-Fat Diet-Induced Obese (DIO) and DIO Plus CCl4-Induced NASH Mice and the Effect of Obeticholic Acid

文献类型：期刊论文

作者Zhu, Nanlin1; Huang, Suling2; Zhang, Qingli1; Zhao, Zhuohui2,3; Qu, Hui2; Ning, Mengmeng2; Leng, Ying2; Liu, Jia1
刊名METABOLITES
出版日期2021-06-10
卷号11期号:6页码:374
关键词nonalcoholic fatty liver disease (NAFLD) nonalcoholic fatty liver (NAFL) nonalcoholic steatohepatitis (NASH) differential metabolites metabolic pathways obeticholic acid (OCA)
DOI10.3390/metabo11060374
文献子类Article
英文摘要The pathophysiology of nonalcoholic fatty liver disease (NAFLD) is a complex process involving metabolic and inflammatory changes in livers and other organs, but the pathogenesis is still not well clarified. Two mouse models were established to study metabolic alteration of nonalcoholic fatty liver and nonalcoholic steatohepatitis, respectively. The concentrations of metabolites in serum, liver and intestine content were measured by the AbsoluteIDQ(R) p180 Kit (Biocrates Life Sciences, Innsbruck, Austria). Multivariate statistical methods, pathway analysis, enrichment analysis and correlation analysis were performed to analyze metabolomic data. The metabolic characteristics of liver, serum and intestine content could be distinctly distinguished from each group, indicating the occurrence of metabolic disturbance. Among them, metabolic alteration of liver and intestine content was more significant. Based on the metabolic data of liver, 19 differential metabolites were discovered between DIO and control, 12 between DIO-CCl4 and DIO, and 47 between DIO-CCl4 and normal. These metabolites were mainly associated with aminoacyl-tRNA biosynthesis, nitrogen metabolism, lipid metabolism, glyoxylate and dicarboxylate metabolism, and amino metabolism. Further study revealed that the intervention of obeticholic acid (OCA) could partly reverse the damage of CCl4. The correlation analysis of metabolite levels and clinical parameters showed that phosphatidylcholines were negatively associated with serum alanine aminotransferase, aspartate aminotransferase, NAFLD activity score, and fibrosis score, while lysophosphatidylcholines, sphingomyelins, amino acids, and acylcarnitines shared the reverse pattern. Our study investigated metabolic alteration among control, NAFLD model, and OCA treatment groups, providing preclinical information to understand the mechanism of NAFLD and amelioration of OCA.
WOS关键词NONALCOHOLIC STEATOHEPATITIS ; HEPATIC STEATOSIS ; RECEPTOR AGONIST ; NUCLEAR RECEPTOR ; LIVER-DISEASE ; PHOSPHATIDYLCHOLINE ; IDENTIFICATION ; MULTICENTER ; PROFILES ; INJURY
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000666103200001
出版者MDPI
源URL[http://119.78.100.183/handle/2S10ELR8/309385]  
专题新药研究国家重点实验室
通讯作者Leng, Ying; Liu, Jia
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Nanlin,Huang, Suling,Zhang, Qingli,et al. Metabolomic Study of High-Fat Diet-Induced Obese (DIO) and DIO Plus CCl4-Induced NASH Mice and the Effect of Obeticholic Acid[J]. METABOLITES,2021,11(6):374.
APA Zhu, Nanlin.,Huang, Suling.,Zhang, Qingli.,Zhao, Zhuohui.,Qu, Hui.,...&Liu, Jia.(2021).Metabolomic Study of High-Fat Diet-Induced Obese (DIO) and DIO Plus CCl4-Induced NASH Mice and the Effect of Obeticholic Acid.METABOLITES,11(6),374.
MLA Zhu, Nanlin,et al."Metabolomic Study of High-Fat Diet-Induced Obese (DIO) and DIO Plus CCl4-Induced NASH Mice and the Effect of Obeticholic Acid".METABOLITES 11.6(2021):374.

入库方式： OAI收割

来源：上海药物研究所

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