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

Sep 28, 2019World journal of gastroenterology

Allyl isothiocyanate reduces fat buildup and inflammation in fatty liver disease through energy regulation and inflammation control pathways

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Abstract

Allyl isothiocyanate (AITC) significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels in mice with nonalcoholic fatty liver disease.

AITC alleviated high fat diet-induced weight gain and liver inflammation in mice.
The treatment led to decreased hepatic lipid accumulation.
AITC downregulated proteins associated with fat production while upregulating proteins involved in fat breakdown.
Inhibition of the NF-κB signaling pathway was observed with AITC treatment.
Knockdown of Sirt1 or AMPKα in liver cells abolished the lipid-lowering effects of AITC.

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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. 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 cellsthrough 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. in vivo in vitro

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.

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

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