Tangshen Formula Alleviates Hepatic Steatosis by Inducing Autophagy Through the AMPK/SIRT1 Pathway

Tangshen Formula Alleviates Hepatic Steatosis by Inducing Autophagy Through the AMPK/SIRT1 Pathway
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糖肾方通过 AMPK/SIRT1 途径诱导自噬减轻肝脏脂肪变性

DOI:
10.3389/fphys.2019.00494
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发表时间:
2019-04
影响因子:
4
通讯作者:
Li Ping
Li Ping
中科院分区:
医学2区
文献类型:
--
作者:
Wang Yan;Zhao Hailing;Li Xin;Li Nan;Wang Qian;Liu Yanzhen;Peng Liang;Li Ping

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糖肾方(TSF)是一种中草药配方,可改善糖尿病肾病人和动物的脂质代谢。然而,TSF对非酒精性脂肪性肝病(NAFLD)的作用和机制尚不清楚。自噬的激活似乎是改善NAFLD的潜在机制。在本研究中,我们研究了TSF对肝脂肪变性的治疗作用,并试图探索其作用是否与激活自噬有关。在这里,我们发现TSF治疗显著减弱了高脂饮食(HFD)和蛋氨酸胆碱缺乏饮食(MCDD)喂养小鼠的肝脏脂肪变性。同时,TSF减少棕榈酸(PA)刺激的HepG 2细胞和原代小鼠肝细胞中的脂质蓄积。此外,TSF增加Sirtuin 1(SIRT 1)的表达,并促进体内自噬激活。TSF还改善PA诱导的SIRT 1表达和SIRT 1依赖性自噬的抑制,从而减轻体外细胞内脂质积聚。此外,TSF增加SIRT 1的表达,并诱导自噬的腺苷一磷酸活化蛋白激酶(AMPK)依赖的方式。此外,SIRT 1敲低取消自噬诱导和降脂作用的TSF。总之,TSF通过诱导AMPK/SIRT 1通路介导的自噬来改善脂质积聚和肝脏脂肪变性。
Tangshen formula (TSF), a formula of Chinese herbal medicine, improves lipid metabolism in humans and animals with diabetic kidney disease. However, the effect and mechanism of TSF on nonalcoholic fatty liver disease (NAFLD) remain unclear. The activation of autophagy appears to be a potential mechanism for improving NAFLD. In the present study, we examined the therapeutic effect of TSF on hepatic steatosis and sought to explore whether its effect is related to activating autophagy. Here, we showed that TSF treatment significantly attenuated hepatic steatosis in both high-fat diet (HFD) and methionine choline-deficient diet (MCDD)-fed mice. Meanwhile, TSF reduced lipid accumulation in palmitate (PA)-stimulated HepG2 cells and primary mouse hepatocytes. Furthermore, TSF increased Sirtuin 1 (SIRT1) expression and promoted autophagy activation in vivo. TSF also improved PA-induced suppression of both SIRT1 expression and SIRT1-dependent autophagy, thereby alleviating intracellular lipid accumulation in vitro. In addition, TSF increased SIRT1 expression and induced autophagy in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner. Moreover, SIRT1 knockdown abolished the autophagy-inducing and lipid-lowering effects of TSF. In conclusion, TSF improved lipid accumulation and hepatic steatosis by inducing the AMPK/SIRT1 pathway-mediated autophagy.
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