Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways  

作　　者：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 

机构地区：[1]Department of Gastroenterology,the First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310003,Zhejiang Province,China [2]Clinical Research Center for Hepatobiliary and Pancreatic Diseases of Zhejiang Province,Hangzhou 310003,Zhejiang Province,China

出　　处：《World Journal of Gastroenterology》2019年第34期5120-5133,共14页世界胃肠病学杂志（英文版）

基　　金：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;Zhejiang Medical Science and Technology Project,No.2017193668

摘　　要：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 200μM 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(20μmol/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 acidβ-oxidation,as well as the upstream mediators Sirtuin 1(Sirt1)and AMPactivated protein kinaseα(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 AMPKαin 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.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, C57 BL/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 AMPactivated 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.

关 键 词：ALLYL ISOTHIOCYANATE NONALCOHOLIC fatty LIVER disease Hepatic STEATOSIS LIVER INFLAMMATION 

分 类 号：R575.5[医药卫生—消化系统]