Aim
To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease (commonly referred to as 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.
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.
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 element-binding 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.