Acanthoic acid suppresses lipin1/2 via TLR4 and IRAK4 signalling pathways in EtOH- and lipopolysaccharide-induced hepatic lipogenesis
Acanthoic acid suppresses lipin1/2 via TLR4 and IRAK4 signalling pathways in EtOH- and lipopolysaccharide-induced hepatic lipogenesis
复制标题
在 EtOH 和脂多糖诱导的肝脏脂肪生成中，棘皮酸通过 TLR4 和 IRAK4 信号通路抑制 lipin1/2
DOI：
10.1111/jphp.12877
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发表时间：
2018-03-01
影响因子：
3.3
通讯作者：
Wu, Yan-Ling
中科院分区：
文献类型：
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作者：
Song, Jian;Han, Xin;Wu, Yan-Ling
目的酒精性肝病时，酒精和脂多糖（LPS）是肝脏脂肪生成的主要刺激因素。我们的目的是确定棘酸（AA）在EtOH和LPS诱导的肝脂肪genes.MethodsHSC-T6细胞的保护机制，乙醇（200毫米）加LPS（1 μ g/ml）处理1小时，然后AA（10或20毫米）为另一个6小时。C57 BL/6小鼠用AA（20和40 mg/kg）或等体积的生理盐水预处理，然后在24 h内暴露于三个剂量的乙醇（5 g/kg体重）。关键发现：异硫氰酸酯能显著降低乙醇/LPS诱导的小鼠脂肪滴形成，减少β-SMA、I型胶原、SREBP-1和lipin 1/2的表达。AA处理可降低EtOH/LPS诱导的HSC细胞TLR 4、CD 14、IRAK 4、TRAF 3、p-TAK 1和NF-B蛋白表达。结论AA可能通过TLR 4和IRAK 4信号通路降低lipin 1/2，从而调节酒精联合LPS诱导的HSC-T6细胞肝纤维化和脂质沉积，AA可能是酒精性肝病的潜在治疗药物。
ObjectivesIn alcoholic liver disease, alcohol and lipopolysaccharide (LPS) are major stimulation factors of hepatic lipogenesis. Our objective was to determine the protective mechanism of acanthoic acid (AA) in EtOH- and LPS-induced hepatic lipogenesis.MethodsHSC-T6 cells were treated with ethanol (200 mm) plus LPS (1 g/ml) for 1 h, followed by AA (10 or 20 m) for another 6 h. C57BL/6 mice were pretreated with of AA (20 and 40 mg/kg) or equal volume of saline and then exposed to three doses of ethanol (5 g/kg body weight) within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing.Key findingsAcanthoic acid significantly decreased the expressions of -SMA, collagen-I, SREBP-1, and lipin1/2 induced, also decreased fat droplets caused by EtOH/LPS. AA treatment decreased the protein expressions of TLR4, CD14, IRAK4, TRAF3, p-TAK1 and NF-B increased by EtOH/LPS on HSC cells. Results in vivo were consistent with results in vitro.ConclusionsOur data demonstrated that AA might modulate hepatic fibrosis and lipid deposition in HSC-T6 cell stimulated with ethanol combined with LPS by decreasing lipin1/2 via TLR4 and IRAK4 signalling pathways, and AA might be considered as a potential therapeutic candidate for alcoholic liver disease.