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
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.
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.
To validate the effect of AITC on NAFLD and clarify the possible mechanism of action.
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.
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.
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.
Plant compounds such as AITC should be further explored for their potential effective activity in NAFLD.