Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways
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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异硫氰酸烯丙酯通过 Sirt1/AMPK 和 NF-kappa B 信号通路改善非酒精性脂肪肝疾病中的脂质积累和炎症
DOI：
10.3748/wjg.v25.i34.5120
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发表时间：
2019-09-14
影响因子：
4.3
通讯作者：
Li, You-Ming
中科院分区：
文献类型：
--
作者：
Li, Chun-Xiao;Gao, Jian-Guo;Li, You-Ming
异硫氰酸丙烯酯（AITC）是一种经典的抗炎和抗肿瘤药物，最近被确定为治疗肥胖和胰岛素抵抗的潜在药物。然而，人们对其对肝脏的直接影响知之甚少。目的：探讨AITC在非酒精性脂肪性肝病（俗称NAFLD）中的作用及其机制。方法采用高脂饲料（HFD）喂养C57BL/6小鼠8周，用200 μ M棕榈酸处理AML-12细胞24 h，用AITC （100 mg/kg/d）口服，用AITC （20 μ mol/L）处理AML-12细胞，建立NAFLD小鼠及细胞模型。结果saitc可显著改善hfd诱导的体重增加、肝脏脂质积累和体内炎症。此外，aitc处理小鼠血清丙氨酸转氨酶和天冬氨酸转氨酶水平显著降低。在机制上，AITC显著下调了hfd喂养小鼠肝脏中固醇调节元件结合蛋白1 （SREBP1）及其脂肪生成靶基因的蛋白水平，上调了脂肪酸β -氧化相关蛋白以及上游介质Sirtuin 1 （Sirt1）和amp活化蛋白激酶α (AMPK α)的水平。AITC还能减弱核因子κ B （nf - κ B）信号通路。一致地，AITC通过Sirt1/AMPK和NF-kappa B信号通路缓解棕榈酸诱导的AML-12细胞脂质积累和炎症。重要的是，进一步的研究表明，在AML-12细胞中，通过sirna介导的Sirt1或AMPKa的下调，AITC对脂质积累的疗效被取消。结论aitc通过激活Sirt1/AMPK通路和抑制NF-kappa B通路，显著改善肝脏脂肪变性和炎症。因此，AITC是一种潜在的治疗NAFLD的药物。
BACKGROUNDAllyl 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.AIMTo investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease (commonly referred to as NAFLD).METHODSTo 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 mu M 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 mu mol/L).RESULTSAITC 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 beta-oxidation, as well as the upstream mediators Sirtuin 1 (Sirt1) and AMP-activated protein kinase alpha (AMPK alpha), in the livers of HFD-fed mice. AITC also attenuated the nuclear factor kappa B (NF-kappa B) signaling pathway. Consistently, AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-kappa B 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 AMPKa in AML-12 cells.CONCLUSIONAITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-kappa B pathway. Therefore, AITC is a potential therapeutic agent for NAFLD.