NDLI: Comprehensive analysis of alterations in lipid and bile acid metabolism by carbon tetrachloride using integrated transcriptomics and metabolomics

Content Provider	Springer Nature Link
Author	Sun, Jinchun Schmitt, Thomas Schnackenberg, Laura K. Pence, Lisa Ando, Yosuke Greenhaw, James Yang, Xi Slavov, Svetoslav Davis, Kelly Salminen, William F. Mendrick, Donna L. Beger, Richard D.
Copyright Year	2014
Abstract	Understanding mechanisms of liver injury can enable better preclinical testing and clinical management of patients. Carbon tetrachloride (CCl$_{4}$), used extensively as a model hepatotoxicant, induces lipid perturbation and increases in plasma bile acids (BAs). An integrated transcriptomics and metabolomics approach was employed to investigate CCl$_{4}$-induced alterations in lipid and BA metabolism. Sprague–Dawley rats were treated orally with corn oil, 50 (low dose, LD) or 2,000 mg CCl$_{4}$/kg/d (high dose, HD). Animals were sacrificed at 6, 24 or 72 h. Terminal blood was collected for clinical chemistry and metabolomics analyses. Livers were harvested for histopathology, metabolomics and transcriptomics analyses. Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the treated groups with the greatest increases observed in the HD group at 24 and 72 h. Blood cholesterol and triglycerides (TGs) were significantly decreased in the HD group at both 24 and 72 h, and hepatocyte vacuolization was observed at these timepoints. Consistent with the clinical chemistry and histopathological data, metabolomics results showed that levels of total fatty acids increased in the liver but decreased in the blood in the HD group at the 24 and 72 h timepoints. This suggested that lipids accumulate in the liver. Primary BAs increased in both liver and blood, while secondary and conjugated BAs decreased in the liver and increased in the blood, which indicated that the BA conjugation pathway and that BA uptake by the liver were inhibited by CCl$_{4}$. Results from this study provide a better understanding of the mechanisms of CCl$_{4}$-induced hepatotoxicity.
Starting Page	1293
Ending Page	1304
Page Count	12
File Format	PDF
ISSN	15733882
Journal	Metabolomics
Volume Number	10
Issue Number	6
e-ISSN	15733890
Language	English
Publisher	Springer US
Publisher Date	2014-05-06
Publisher Institution	Metabolomics Society
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Metabolomics Transcriptomics Carbon tetrachloride Hepatotoxicity Lipid pathway Bile acid pathway Biochemistry Molecular Medicine Cell Biology Developmental Biology Biomedicine
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Metabolomics and biomarker discovery: NMR spectral data of urine and hepatotoxicity by carbon tetrachloride, acetaminophen, and d-galactosamine in rats

Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

Transient decrease of hepatic NAD$^{+}$ and amino acid alterations during treatment with valproate: new insights on drug-induced effects in vivo using targeted MS-based metabolomics

Metabolomics reveals alterations of serotonin pathway in carriers of NOS1AP variant rs12742393

MarVis-Pathway: integrative and exploratory pathway analysis of non-targeted metabolomics data

Exposure to perfluorononanoic acid combined with a low-dose mixture of 14 human-relevant compounds disturbs energy/lipid homeostasis in rats

De novo synthesize of bile acids in pulmonary arterial hypertension lung

Integration of untargeted metabolomics with transcriptomics reveals active metabolic pathways

Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington’s disease peripheral blood samples

Comprehensive analysis of alterations in lipid and bile acid metabolism by carbon tetrachloride using integrated transcriptomics and metabolomics

Similar Documents

Metabolomics and biomarker discovery: NMR spectral data of urine and hepatotoxicity by carbon tetrachloride, acetaminophen, and d-galactosamine in rats

Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

Transient decrease of hepatic NAD$^{+}$ and amino acid alterations during treatment with valproate: new insights on drug-induced effects in vivo using targeted MS-based metabolomics

Metabolomics reveals alterations of serotonin pathway in carriers of NOS1AP variant rs12742393

MarVis-Pathway: integrative and exploratory pathway analysis of non-targeted metabolomics data

Exposure to perfluorononanoic acid combined with a low-dose mixture of 14 human-relevant compounds disturbs energy/lipid homeostasis in rats

De novo synthesize of bile acids in pulmonary arterial hypertension lung

Integration of untargeted metabolomics with transcriptomics reveals active metabolic pathways

Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington’s disease peripheral blood samples

Comprehensive analysis of alterations in lipid and bile acid metabolism by carbon tetrachloride using integrated transcriptomics and metabolomics