Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2019; 25(34): 5120-5133
Published online Sep 14, 2019. doi: 10.3748/wjg.v25.i34.5120
Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways
Chun-Xiao Li, Jian-Guo Gao, Xing-Yong Wan, Yi Chen, Cheng-Fu Xu, Ze-Min Feng, Hang Zeng, Yi-Ming Lin, Han Ma, Ping Xu, Chao-Hui Yu, You-Ming Li
Chun-Xiao Li, Jian-Guo Gao, Xing-Yong Wan, Yi Chen, Cheng-Fu Xu, Ze-Min Feng, Hang Zeng, Yi-Ming Lin, Han Ma, Ping Xu, Chao-Hui Yu, You-Ming Li, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Chao-Hui Yu, Clinical Research Center for Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
Author contributions: Li CX and Gao JG designed and performed the study; Wan XY, Chen Y, Xu CF and Feng ZM performed the research; Lin YM and Yu CH analyzed the data; Ma H and Xu P provided guidance during revision; Li YM supervised the study and provided consultation during the entire study.
Supported by Natural Science Foundation of China, No. 81700504 and No. 81700511; Science Foundation of Health Bureau of Zhejiang Province, No. 2017183691; Natural Science Foundation of Zhejiang Province, No. LY17H030006 and No. LQ15H030002; and Zhejiang Medical Science and Technology Project, No. 2017193668.
Institutional review board statement: The study was reviewed and approved by the review board of Zhejiang University School of Medicine, Zhejiang Province, China.
Institutional animal care and use committee statement: All experiments were conducted with approval of the First Affiliated Hospital of Zhejiang University Institutional Animal Care and Use Committee (Permit number: 2016-231).
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines and prepared and revised the manuscript 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 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: You-Ming Li, PhD, Professor, Chief Doctor, Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. zlym@zju.edu.cn
Telephone: +86-571-87236863 Fax: +86-571-87236863
Received: April 2, 2019
Peer-review started: April 2, 2019
First decision: May 27, 2019
Revised: June 12, 2019
Accepted: June 25, 2019
Article in press: June 26, 2019
Published online: September 14, 2019
ARTICLE HIGHLIGHTS
Research background

Nonalcoholic fatty liver disease (NAFLD) is an unmet medical need with no approved therapies. Recent studies have shown that allyl isothiocyanate (AITC) has a potential protective effect on obesity and insulin resistance. The evaluation of the effect of AITC on NAFLD as well as the mechanism of action may provide a new therapeutic trend.

Research motivation

Emerging evidence suggests a beneficial role for AITC in inflammation, cancer, diet-induced obesity and insulin resistance. Enhanced lipolysis in adipocytes and intensified hydrolysis of triglyceride in the serum of rats treated with AITC was also reported. As little is known about its direct impact on liver or its underlying mechanism, it is imperative to characterize the potential effect of AITC on NAFLD.

Research objectives

To validate the effect of AITC on NAFLD and clarify the possible mechanism of action.

Research methods

C57BL/6 mice were fed a high fat diet (HFD) for 8 wk, and AML-12 cells were treated with 200 μmol/L palmitate acid (PA) for 24 h to establish in vivo and in vitro models of hepatic steatosis. Mice were administered AITC (100 mg/kg/d) orally and AML-12 cells were treated with AITC (20 μmol/L) to detect the effect of AITC on NAFLD.

Research results

Our results show that AITC significantly ameliorates HFD-induced weight gain, hepatic lipid accumulation, inflammation, and PA-induced lipid accumulation as well as inflammation in AML-12 cells, accompanied by activated Sirt1/AMPK and inhibited NF-κB signaling pathways. The curative effect of AITC on lipid accumulation is abolished by siRNA-mediated knockdown of either Sirt1 or AMPKα in AML-12 cells.

Research conclusions

AITC treatment protects against HFD and PA-induced lipid accumulation and inflammation in vivo and in vitro. These effects are associated with Sirt1/AMPK and NF-κB signaling pathways.

Research perspectives

Plant compounds such as AITC should be further explored for their potential effective activity in NAFLD.