Published online Sep 14, 2019. doi: 10.3748/wjg.v25.i34.5120
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
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.
To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease (commonly referred to as NAFLD).
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).
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.
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.
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.