Dataset Information

Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis.

ABSTRACT: Lithocholic acid (LCA), alpha-naphthyl isothiocyanate (ANIT), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and ethinyl estradiol (EE) are four commonly used chemicals for the construction of acute intrahepatic cholestasis. In order to better understand the mechanisms of acute cholestasis caused by these chemicals, the metabolic characteristics of each model were summarized using lipidomics and metabolomics techniques. The results showed that the bile acid profile was altered in all models. The lipid metabolism phenotype of the LCA group was most similar to that of primary biliary cirrhosis (PBC) patients. The ANIT group and the DDC group had similar metabolic disorder characteristics, which were speculated to be related to hepatocyte necrosis and inflammatory pathway activation. The metabolic profile of the EE group was different from other models, suggesting that estrogen-induced cholestasis had its special mechanism. Ceramide and acylcarnitine accumulation was observed in all model groups, indicating that acute cholestasis was closely related to mitochondrial dysfunction. With a deeper understanding of the mechanism of acute intrahepatic cholestasis, this study also provided a reference for the selection of appropriate chemicals for cholestatic liver disease models.

SUBMITTER: Li W

PROVIDER: S-EPMC9213752 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis.

Li Weiwei W Chen Hui H Qian Yihan Y Wang Shouchuan S Luo Zichen Z Shan Jinjun J Kong Xiaoni X Gao Yueqiu Y

Frontiers in pharmacology 20220608

Lithocholic acid (LCA), alpha-naphthyl isothiocyanate (ANIT), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and ethinyl estradiol (EE) are four commonly used chemicals for the construction of acute intrahepatic cholestasis. In order to better understand the mechanisms of acute cholestasis caused by these chemicals, the metabolic characteristics of each model were summarized using lipidomics and metabolomics techniques. The results showed that the bile acid profile was altered in all models. T ...[more]

PMID: 35754480

Similar Datasets

Project description:BackgroundIntrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and is associated with increased risks in fetal complications. Currently, the exact mechanism of this disease is unknown. The purpose of this study was to develop potential biomarkers for the diagnosis and prediction of ICP.MethodsWe enrolled 40 pregnant women diagnosed with ICP and 40 healthy pregnant controls. The number of placental samples and serum samples between the two groups was 10 and 40 respectively. Ultra-performance liquid chromatography tandem high-resolution mass spectrometry was used to analyze placental metabolomics. Then, we verified the differentially expressed proteins and metabolites, both placental and blood serum, in the first, second, and third trimesters.ResultsMetabolomic analysis of placental tissue revealed that fatty acid metabolism and primary bile acid biosynthesis were enriched. In the integrated proteomic and metabolomic analysis of placental tissue, peroxisomal acyl-CoA oxidase 1 (ACOX1), L-palmitoylcarnitine, and glycocholic acid were found to be three potential biomarkers. In a follow-up analysis, expression levels of both placental and serum ACOX1, L-palmitoylcarnitine, and glycocholic acid in both placenta and serum were found to be significantly higher in third-trimester ICP patients; the areas under the ROC curves were 0.823, 0.896, and 0.985, respectively. Expression levels of serum ACOX1, L-palmitoylcarnitine, and glycocholic acid were also significantly higher in first- and second-trimester ICP patients; the areas under the ROC curves were 0.726, 0.657, and 0.686 in the first trimester and 0.718, 0.727, and 0.670 in the second trimester, respectively. Together, levels of the three aforementioned biomarkers increased the value for diagnosing and predicting ICP (AUC: 0.993 for the third, 0.891 for the second, and 0.932 for the first trimesters).ConclusionsL-palmitoylcarnitine, ACOX1, and glycocholic acid levels taken together may serve as a new biomarker set for the diagnosis and prediction of ICP.

Dataset Information

Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis.

Publications

Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets