Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway.
Salidroside Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease via AMPK-Dependent TXNIP/NLRP3 Pathway.
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红景天苷通过 AMPK 依赖性 TXNIP/NLRP3 途径减轻高脂饮食诱发的非酒精性脂肪肝
DOI：
10.1155/2018/8597897
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发表时间：
2018
影响因子：
--
通讯作者：
Jin S
中科院分区：
文献类型：
--
作者：
Zheng T;Yang X;Li W;Wang Q;Chen L;Wu D;Bian F;Xing S;Jin S
我们以前的研究表明，红景天苷可以减轻C57BLKS/Leprdb(db/db)2型糖尿病小鼠的肝脏脂肪变性。本研究旨在探讨红景天苷对高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)的治疗作用。用高脂饮食或常规饲料喂养小鼠，随机分为两组，分别给予红景天苷或赋形剂治疗8周。然后在体内和体外进行生化分析和组织病理学检查。红景天苷可减轻HFD诱导的肥胖、血糖变异性和肝脏脂肪沉积，显著增加HFD小鼠的胰岛素敏感性。此外，红景天苷抑制氧化应激、硫氧还蛋白相互作用蛋白(TXNIP)的表达，以及肝脏中NLRP3炎症体的激活。在培养的肝细胞中，红景天苷剂量依赖地调节脂质堆积、活性氧(ROS)的产生和NLRP3炎症体的激活，以及改善AMP激活的蛋白激酶(AMPK)活性和胰岛素敏感性。通过抑制AMPK的激活或小干扰RNA(SiRNA)的作用，可抑制红景天苷对肝细胞的有益作用。我们的研究结果表明，红景天苷通过改善肝脏脂代谢和NLRP3炎性小体激活来保护NAFLD，这些作用与调节氧化应激和AMPK依赖的TXNIP/NLRP3通路有关。
Our previous studies suggested that salidroside could alleviate hepatic steatosis in type 2 diabetic C57BLKS/Leprdb (db/db) mice. The aim of the present study was to evaluate the therapeutic effect of salidroside on high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD) by investigating underlying mechanisms. Mice were fed with HFD or regular diet, randomly divided into two groups, and treated with salidroside or vehicle for 8 weeks. Then, biochemical analyses and histopathological examinations were conducted in vivo and in vitro. Salidroside administration attenuated HFD-induced obesity, blood glucose variability, and hepatic lipid deposition, markedly increasing insulin sensitivity in HFD mice. In addition, salidroside suppressed oxidative stress, thioredoxin-interacting protein (TXNIP) expression, and NLRP3 inflammasome activation in the liver. In cultured hepatocytes, salidroside dose dependently regulated lipid accumulation, reactive oxygen species (ROS) generation, and NLRP3 inflammasome activation as well as improved AMP-activated protein kinase (AMPK) activity and insulin sensitivity. The inhibition of AMPK activation by inhibitor or short interfering RNA (siRNA) resulted in the suppression of the beneficial effects of salidroside in hepatocytes. Our findings demonstrated that salidroside protects against NAFLD by improving hepatic lipid metabolism and NLRP3 inflammasome activation, and these actions are related to the regulation of the oxidative stress and AMPK-dependent TXNIP/NLRP3 pathways.
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影响因子：
3.7
作者：
Dixon LJ;Flask CA;Papouchado BG;Feldstein AE;Nagy LE
通讯作者：
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影响因子：
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通讯作者：
Bassett DS