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
Abstract
AIM

To evaluate whether fish oil (FO) can protect liver injury induced by intestinal ischemia/reperfusion (I/R) via the AMPK/SIRT-1/autophagy pathway.

METHODS

Ischemia in Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of FO emulsion or normal saline was administered by intraperitoneal injection for 5 consecutive days to each animal. Animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analyses. AMPK, SIRT-1, and Beclin-1 expression was determined in lipopolysaccharide (LPS)-stimulated HepG2 cells with or without FO emulsion treatment.

RESULTS

Intestinal I/R induced significant liver morphological changes and increased serum alanine aminotransferase and aspartate aminotransferase levels. Expression of p-AMPK/AMPK, SIRT-1, and autophagy markers was decreased whereas tumor necrosis factor-α (TNF-α) and malonaldehyde (MDA) were increased. FO emulsion blocked the changes of the above indicators effectively. Besides, in LPS-stimulated HepG2 cells, small interfering RNA (siRNA) targeting AMPK impaired the FO induced increase of p-AMPK, SIRT-1, and Beclin-1 and decrease of TNF-α and MDA. SIRT-1 siRNA impaired the increase of SIRT-1 and Beclin-1 and the decrease of TNF-α and MDA.

CONCLUSION

Our study indicates that FO may protect the liver against intestinal I/R induced injury through the AMPK/SIRT-1/autophagy pathway.

Keywords: Fish oil; AMPK/SIRT1/autophagy; Liver injury; Intestinal ischemia/reperfusion

Core tip: Intestinal ischemia/reperfusion (I/R) injury is a remarkable problem in many clinical conditions. Increased evidence indicates AMPK/SIRT-1 pathway linked autophagy exhibits a protective effect in liver diseases. Fish oil (FO) emulsion improves outcomes in patients with parenteral nutrition associated liver injury. We aimed to evaluate whether FO can protect liver injury induced by intestinal I/R via the AMPK/SIRT-1/autophagy pathway. Our results indicate that FO may protect the liver against intestinal I/R induced injury through the AMPK/SIRT-1/autophagy pathway. To our knowledge, we maybe for the first time present that FO attenuated intestinal I/R induced liver injury by inducing autophagy both in vivo and in vitro through the AMPK/SIRT-1 signaling pathway.