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
Processing time: 163 Days and 17.2 Hours
Abstract
BACKGROUND

Allyl isothiocyanate (AITC), a classic anti-inflammatory and antitumorigenic agent, was recently identified as a potential treatment for obesity and insulin resistance. However, little is known about its direct impact on the liver.

AIM

To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease (commonly referred to as NAFLD).

METHODS

To establish a mouse and cellular model of NAFLD, C57BL/6 mice were fed a high fat diet (HFD) for 8 wk, and AML-12 cells were treated with 200 μM palmitate acid for 24 h. For AITC treatment, mice were administered AITC (100 mg/kg/d) orally and AML-12 cells were treated with AITC (20 μmol/L).

RESULTS

AITC significantly ameliorated HFD-induced weight gain, hepatic lipid accumulation and inflammation in vivo. Furthermore, serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice. Mechanistically, AITC significantly downregulated the protein levels of sterol regulatory element­binding protein 1 (SREBP1) and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acid β-oxidation, as well as the upstream mediators Sirtuin 1 (Sirt1) and AMP-activated protein kinase α (AMPKα), in the livers of HFD-fed mice. AITC also attenuated the nuclear factor kappa B (NF-κB) signaling pathway. Consistently, AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways. Importantly, further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKα in AML-12 cells.

CONCLUSION

AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway. Therefore, AITC is a potential therapeutic agent for NAFLD.

Keywords: Allyl isothiocyanate; Nonalcoholic fatty liver disease; Hepatic steatosis; Liver inflammation

Core tip: Nonalcoholic fatty liver disease (NAFLD) is rapidly prevalent as a remarkable problem worldwide. We aimed to investigate the therapeutic role of allyl isothiocyanate (AITC) in lipid accumulation and inflammation during NAFLD development in mice fed a high fat diet and AML-12 cells treated with palmitate acid. Our study for the first time demonstrates that AITC ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK and IKK/NF-κB signaling pathway. This study reveals role for AITC as a potential therapeutic agent for NAFLD.