Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2020; 26(46): 7299-7311
Published online Dec 14, 2020. doi: 10.3748/wjg.v26.i46.7299
Untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease induced by high-temperature-processed feed in Sprague-Dawley rats
Li-Jun Xue, Ju-Qiang Han, Yuan-Chen Zhou, Hong-Ye Peng, Teng-Fei Yin, Kai-Min Li, Shu-Kun Yao
Li-Jun Xue, Shu-Kun Yao, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
Ju-Qiang Han, Department of Hepatology, The Seventh Medical Center of PLA General Hospital, Beijing 100700, China
Yuan-Chen Zhou, Hong-Ye Peng, Teng-Fei Yin, Kai-Min Li, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Author contributions: Xue LJ, Zhou YC, Peng HY and Yin TF performed the experiments; Xue LJ analyzed the data, prepared figures and contributed to the drafting of the manuscript; Yao SK and Han JQ supervised this work and edited and revised manuscript; Yao SK initiated the project, design the experiments and approved the final version of manuscript; Li KM provided technical assistance; All authors read and approved the final manuscript.
Supported by Science and Technology Project Task Book of Beijing, No. Z171100001717008.
Institutional animal care and use committee statement: The study was approved by the Animal Care Committees at China-Japan Friendship Hospital (Approval No: 190201).
Conflict-of-interest statement: All authors report no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the first author at
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Shu-Kun Yao, MD, PhD, Professor, Department of Gastroenterology, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Chaoyang District, Beijing 100029, China.
Received: August 17, 2020
Peer-review started: August 17, 2020
First decision: October 18, 2020
Revised: October 27, 2020
Accepted: November 9, 2020
Article in press: November 9, 2020
Published online: December 14, 2020
Research background

Nonalcoholic fatty liver disease (NAFLD) has surpassed viral hepatitis to become the most common liver disease in China and is facing increasing challenges in prevention and treatment. The etiology of nonobese NAFLD has not been fully elucidated and is often neglected clinically. For patients with normal body mass index and no abnormal serological indicators, liver damage may have occurred, which should be given full attention by clinicians. It is of great significance to develop new animal models to study the pathogenesis of this disease.

Research motivation

In modern society, more and more young people suffer from fatty liver disease with normal body mass index. They prefer high temperature processed food such as barbecue, hot pot and fried food, which may be associated with the development of nonobese NAFLD.

Research objectives

The purpose of our study was to investigate the effects of high-temperature-processed feed on rats and to explore the metabolomics pathogenesis of nonobese NAFLD.

Research methods

Fifty-four male Sprague-Dawley rats were divided into three groups: The control group received a standard diet; the nonfried soybeans (NDFS) group received 60% nonfried soybeans and 40% basal feed and the dry-fried soybeans (DFS) group received 60% dry-fried soybeans and 40% basal feed. Six rats were sacrificed at weeks 4, 8 and 12 in each group. The food intake, body weight, Lee’s index, liver index, serological index and hepatic histopathology were assessed. Untargeted metabolomics characteristics were used to analyze the changes in liver metabolites of rats at week 12. Correlations between selected metabolites and pathology scores between the DFS and control groups and between the DFS and NDFS groups were analyzed. The results of correlation analysis in this study were determined by P < 0.05 and absolute value of correlation coefficient greater than or equal to 0.5.

Research results

There was no statistically significant difference in the food intake, body weight, Lee's index or serological index between the DFS group and the control group (P > 0.05). At week 8 and week 12, the steatosis score in the DFS group were significantly higher than those in the other two groups (P < 0.05). At week 12, the fibrosis score in the DFS group was significantly higher than those in the other two groups (P < 0.05). The correlation analysis of the liver pathology score and differential metabolites in the DFS and NDFS groups showed that there were 10 strongly correlated substances: Five positively correlated substances and five negatively correlated substances. The correlation analysis of the liver pathology score and differential metabolites in the DFS and control groups showed that there were 13 strongly correlated substances: Four positively correlated substances and nine negatively correlated substances.

Research conclusions

We successfully induced liver damage in rats by using a specially prepared high-temperature-processed feed and preliminarily explored the untargeted metabolomics characteristics. Our study provides new insights into the diagnosis, treatment and health education of patients with NAFLD.

Research perspectives

In the future, we will further study the molecular mechanism of fatty liver induced by high-temperature-processed feed in rats and explore the effects of other high-temperature-processed feed on rat liver.