Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2019; 25(8): 941-954
Published online Feb 28, 2019. doi: 10.3748/wjg.v25.i8.941
Dynamic changes of key metabolites during liver fibrosis in rats
Jiong Yu, Jian-Qin He, De-Ying Chen, Qiao-Ling Pan, Jin-Feng Yang, Hong-Cui Cao, Lan-Juan Li
Jiong Yu, Jian-Qin He, De-Ying Chen, Qiao-Ling Pan, Jin-Feng Yang, Hong-Cui Cao, Lan-Juan Li, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
Author contributions: Li LJ and Cao HC conceived and designed the study; Yu J wrote the manuscript and performed the statistical analysis; Chen DY substantially contributed to the conception and design of the study as well as the acquisition, analysis, and interpretation of the data; Yu J and Pan QL performed the immunohistochemical detection, RT-PCR, and data collection; He JQ provided technical support and revised the manuscript; all authors reviewed and approved the final version of the manuscript.
Supported by the Stem Cell and Translational Research, the National Key Research and Development Program of China, No. 2016YFA0101001; and Independent Project Fund of the State Key Laboratory for Diagnosis and Treatment of Infectious Disease (SKL DTID).
Institutional review board statement: This study was reviewed and approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University (No. 201543).
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The ARRIVE Guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Lan-Juan Li, MD, PhD, Academic Research, Doctor, Professor, Senior Researcher, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. ljli@zju.edu.cn
Telephone: +86-571-87236458 Fax: +86-571-87236459
Received: November 20, 2018
Peer-review started: November 20, 2018
First decision: December 12, 2018
Revised: January 10, 2019
Accepted: January 28, 2019
Article in press: January 28, 2019
Published online: February 28, 2019
ARTICLE HIGHLIGHTS
Research background

Liver fibrosis is a common chronic progressive liver disease, and alanine aminotransferase is a commonly used diagnostic indicator for liver disease. Magnetic resonance imaging- and ultrasound-based elastography has been used for further assessment of hepatic steatosis and fibrosis, but these techniques are not able to diagnose inflammation and cell damage very well. Therefore, new liver fibrosis and functional biomarkers are needed as supplements.

Research motivation

Metabolomics is an important component of systems biology which provides quantitative measurements of global changes in individual metabolic characteristics in biological fluids responding to a variety of physiological and pathological stimuli, and it can be used to discover new biomarkers for differential diagnosis of disease.

Research objectives

The main objectives were to investigate the dynamic changes in metabolic profiles during the liver fibrosis progression, and seek for potential novel biomarkers for early diagnosis of liver fibrosis.

Research methods

A liver fibrosis model was induced by subcutaneous injection with CCl4. The dynamic changes in metabolic profiles during the progression of liver fibrosis were analyzed by ultra-performance liquid chromatography-mass spectrometry, and independent sample test and receiver operating characteristic analysis were used to identify potential biomarkers.

Research results

A liver fibrosis model was successfully established, which was evaluated by liver chemical tests, liver histopathology, Masson’s trichrome staining, and the expression levels of α-smooth muscle actin and transforming growth factor β1. Principal component analysis and orthogonal partial least squares discriminant analysis were used to characterize the metabolic profiles, which can clearly distinguish early liver fibrosis and advanced groups. We identified 21 metabolites associated with liver fibrosis, and two of them, β-muricholic acid (β-MCA) and cervonoyl ethanolamide (CEA), had excellent diagnostic value.

Research conclusions

The dynamic metabolomics profile is useful for screening early metabolic characteristics associated with progression of fibrosis. Two new metabolic biomarkers identified in this study, β-MCA and CEA, can correctly classify the disease stage in our fibrosis animal model.

Research perspectives

According to the results of rat experiments, further mechanistic studies are needed to investigate the involvement of these metabolites in fibrotic progression. We also need to collect clinical samples for further verification, and the markers identified may be used for clinical diagnosis in the future.