Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2019; 25(45): 6653-6667
Published online Dec 7, 2019. doi: 10.3748/wjg.v25.i45.6653
Irisin attenuates intestinal injury, oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis
Yi-Fan Ren, Meng-Zhou Wang, Jian-Bin Bi, Jia Zhang, Lin Zhang, Wu-Ming Liu, Sha-Sha Wei, Yi Lv, Zheng Wu, Rong-Qian Wu
Yi-Fan Ren, Meng-Zhou Wang, Jian-Bin Bi, Jia Zhang, Lin Zhang, Wu-Ming Liu, Sha-Sha Wei, Yi Lv, Rong-Qian Wu, National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Yi-Fan Ren, Meng-Zhou Wang, Jian-Bin Bi, Jia Zhang, Lin Zhang, Wu-Ming Liu, Yi Lv, Zheng Wu, Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Author contributions: All authors contributed to the study; Ren YF contributed to acquisition of data, analysis and interpretation of data, drafting of the manuscript and statistical analysis; Wang MZ, Zhang J, Bi JB, Zhang L, Liu WM and Wei SS contributed to acquisition of data; Lv Y and Wu Z contributed to critical revision of the manuscript; Wu RQ contributed to study concept and design, drafting of the manuscript and critical revision of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81770491.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Xi’an Jiaotong University.
Institutional animal care and use committee statement: This study was reviewed and approved by the Ethics Committee of the Xi’an Jiaotong University.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.
Data sharing statement: All data generated or analyzed during this study are included in this published article. The data used to support the findings of this study are available from the corresponding author upon request at rwu001@mail.xjtu.edu.cn.
ARRIVE guidelines statement: All of our experiments follow ARRIVE guidelines.
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: Rong-Qian Wu, MD, PhD, Professor, National-Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, 76 West Yanta Road, Xi’an 710061, Shaanxi Province, China. rwu001@mail.xjtu.edu.cn
Telephone: +86-29-82657541 Fax: +86-29-85252580
Received: September 17, 2019
Peer-review started: September 17, 2019
First decision: November 4, 2019
Revised: November 8, 2019
Accepted: November 16, 2019
Article in press: November 16, 2019
Published online: December 7, 2019
Processing time: 79 Days and 23.5 Hours
ARTICLE HIGHLIGHTS
Research background

Acute pancreatitis (AP) is often associated with intestinal injury, which in turn exaggerates the progression of AP. Our recent study has shown that a low level of serum irisin, a novel exercise-induced hormone, is associated with poor outcomes in patients with AP, and irisin administration protects against experimental AP. However, the role of irisin in intestinal injury in AP has not been evaluated.

Research motivation

The main topic of this study was to investigate the effect of irisin administration on intestinal injury in experimental AP. We found that irisin alleviates intestinal cell injury in AP mice by inhibiting oxidative stress and blocking ER stress.

Research objectives

To investigate the effect of irisin administration on intestinal injury in experimental AP. Exogenous irisin can effectively reduce intestinal injury and systemic inflammation in mice with AP. In the future, irisin-related drugs can be developed for intestinal injury of AP.

Research methods

Arginine-AP was induced by two hourly intraperitoneal injections of 4.0 g/kg L-arginine. At 2 h after the last injection of L-arginine, normal saline (vehicle) or 50 μg/kg or 250 μg/kg irisin was administered through intraperitoneal injection. The animals were sacrificed 69 h after irisin treatment (i.e. 72 h after the first injection of L-arginine). Blood and tissue samples were collected. Intestinal injury, apoptosis, oxidative stress, endoplasmic reticulum stress levels as well as systemic inflammation were measured.

Research results

Administration of irisin significantly mitigated intestinal damage, reduced apoptosis, and attenuated oxidative and ER stress in AP mice. In addition, irisin treatment also effectively downregulated serum TNF-α and IL-6 levels and alleviated injury in the pancreas, liver and lung of AP mice. Until now, the exact molecular mechanism by which irisin alleviates intestinal injury in AP remains unknown.

Research conclusions

In this study we report for the first time that irisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP. Irisin has a great potential to be further developed as an effective treatment for patients with AP. In summary, irisin alleviates intestinal cell injury in AP mice by inhibiting oxidative stress and blocking ER stress. We believe that future studies can further explore the specific mechanism of irisin relieving intestinal injury in AP. The present study represents an important step forward in the study of irisin in the treatment of AP-associated intestinal injury.

Research perspectives

In this study, we can learn that the protective effect of exercise on multiple organs can be revealed by modern science. In the future, our research direction should be to further explore the specific mechanism of irisin’s protective effect on intestinal injury of AP and even multiple organs. Future research should start from animal experiments and carry out more clinical studies so that basic science can make contributions to human health as soon as possible.