Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2018; 24(7): 833-843
Published online Feb 21, 2018. doi: 10.3748/wjg.v24.i7.833
Fish oil alleviates liver injury induced by intestinal ischemia/reperfusion via AMPK/SIRT-1/autophagy pathway
Hui-Rong Jing, Fu-Wen Luo, Xing-Ming Liu, Xiao-Feng Tian, Yun Zhou
Hui-Rong Jing, Fu-Wen Luo, Xing-Ming Liu, Xiao-Feng Tian, Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
Yun Zhou, Department of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
Author contributions: Jing HR and Luo FW performed the majority of experiments and almost equally contributed to the present study; Luo FW and Liu XM provided vital reagents and analytical tools and were also involved in editing the manuscript; Jing HR coordinated and provided the collection of all the human material in addition to providing financial support for this work; Tian XF and Zhou Y designed the study and wrote the manuscript.
Supported by the National Natural Science Foundation of China, No. 81600446; Natural Science Foundation of Liaoning Province, China, No. 201102048; and Natural Science Foundation of Dalian Medical Association, No. WSJ/KJC-01-JL-01.
Institutional review board statement: The study was reviewed and approved by the review board of Dalian Medical University, Liaoning Province, China.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Dalian Medical University (Permit number: SCXK 2008-0002).
Conflict-of-interest statement: There is no conflict of interest in this study.
Data sharing statement: No additional data are available.
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/
Correspondence to: Yun Zhou, MD, Doctor, Department of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian 116023, Liaoning Province, China. zydy2ynutrition@126.com
Telephone: +86-411-84690722 Fax: +86-411- 84672130
Received: October 28, 2017
Peer-review started: October 30, 2017
First decision: November 15, 2017
Revised: December 25, 2017
Accepted: January 15, 2018
Article in press: January 15, 2018
Published online: February 21, 2018
Processing time: 102 Days and 21.2 Hours
ARTICLE HIGHLIGHTS
Research background

The liver is the most vulnerable organ after intestinal ischemia/reperfusion (I/R) because the liver and intestine share the anatomical common pathway such as coupled vasculature. The mechanism is obscure and has multiple overlapping pathways. Increased evidence indicates that the AMPK/SIRT-1/autophagy pathway may be involved in this process. Fish oil (FO) may regulate the AMPK/SIRT-1/autophagy pathway to affect liver injury induced by intestinal I/R.

Research motivation

Understanding and regulating AMPK/SIRT-1/autophagy pathway using a safe and effective substance like FO will be an important area of future research.

Research objectives

This study aimed to provide evidence that FO can attenuate intestinal I/R induced liver injury by inducing autophagy through the AMPK/SIRT-1 pathway. This will provide a therapeutic target for future clinical applications of FO to prevent intestinal I/R associated liver disease.

Research methods

This research was performed using Wistar rats challenged by intestinal I/R and HepG2 cells stimulated with LPS to mimic the in vivo pathogenesis. Further, RNA interference has been employed, which laid a foundation for the future gene knockout animal study.

Research results

Intestinal I/R induced apparent liver injury, including histopathological injury and liver dysfunction, and this was associated with increased TNF-α and MDA, and decreased AMPK/SIRT-1/autophagy molecular function. FO emulsion restored the balance of the factors and alleviated liver injury. The similar results were observed in HepG2 cells stimulated with LPS.

Research conclusions

Intestinal I/R induced liver injury is associated with decreased AMPK/SIRT-1/autophagy (LC3 II, Beclin-1, and P62 expression) molecular function. FO emulsion restored the beneficial factors and alleviated liver injury. Similar results were observed in HepG2 cells. We present a novel theory here that FO can prevent intestinal I/R associated liver disease via the AMPK/SIRT-1/autophagy pathway. This may be a potential novel target for patients. We may provide the first evidence of AMPK/SIRT-1/autophagy regulated by FO in liver injury induced by intestinal I/R. Our hypothesis was confirmed using rat models and HepG2 cells treated with LPS and RNA interfere to mimic the conditions in vivo. Thus, FO and FO-related products may have novel clinical applications to prevent intestinal I/R associated liver disease in future.

Research perspectives

This study has some limitations and further studies should be performed using gene knockout animals and clinical application should be concentrated.