Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes.
Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes.
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阿魏酸通过 SIRT1 调节的自噬途径减轻脂毒性诱导的肝细胞死亡，并且独立于 AML-12 肝细胞中的 AMPK 和 Akt。
DOI：
10.1186/s12986-021-00540-9
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发表时间：
2021-01-19
影响因子：
4.5
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Xu T;Song Q;Zhou L;Yang W;Wu X;Qian Q;Chai H;Han Q;Pan H;Dou X;Li S
脂毒性诱导的细胞死亡在代谢性疾病的发病机制中起着有害的作用。阿魏酸是一种广泛存在于植物性食品中的自由基清除剂，具有多种生物活性。然而，阿魏酸对肝脏脂毒性的益处在很大程度上尚不清楚。在这里，我们研究了阿魏酸对棕榈酸诱导的脂毒性的保护作用，并阐明了其在AML-12肝细胞中的潜在机制。将AML-12小鼠肝细胞暴露于棕榈酸酯以模拟脂毒性。在棕榈酸酯处理前2 h加入不同剂量（25、50和100 μM）的阿魏酸。通过测定乳酸脱氢酶释放、细胞核染色和裂解型半胱天冬酶-3的表达来检测细胞活力。用荧光探针分析细胞内活性氧含量和线粒体膜电位。通过Western blotting和实时荧光定量PCR等分子生物学方法对该作用机制进行了初步探讨，并通过siRNA干扰进一步验证了该作用机制。我们的数据表明，阿魏酸显着抑制棕榈酸诱导的细胞死亡，挽救线粒体膜电位，减少活性氧的积累，并减少炎症因子的激活，包括IL-6和IL-1 β。阿魏酸显著刺激肝细胞自噬，而自噬抑制阻断阿魏酸对脂毒性的保护作用。阿魏酸激活的自噬，这是由SIRT 1上调触发，在其抗脂毒性作用的机制。SIRT 1沉默阻断了阿魏酸诱导的大多数有益变化。我们证明了植物性食品中发现的植物化学物质阿魏酸通过SIRT 1/自噬途径保护肝脏免受脂毒性。增加富含阿魏酸的食物的摄入是预防和/或改善以脂毒性为典型病理特征的代谢性疾病的潜在策略。
Lipotoxicity-induced cell death plays a detrimental role in the pathogenesis of metabolic diseases. Ferulic acid, widespread in plant-based food, is a radical scavenger with multiple bioactivities. However, the benefits of ferulic acid against hepatic lipotoxicity are largely unclear. Here, we investigated the protective effect of ferulic acid against palmitate-induced lipotoxicity and clarified its potential mechanisms in AML-12 hepatocytes. AML-12 mouse hepatocytes were exposed to palmitate to mimic lipotoxicity. Different doses (25, 50, and 100 μM) of ferulic acid were added 2 h before palmitate treatment. Cell viability was detected by measuring lactate dehydrogenase release, nuclear staining, and the expression of cleaved-caspase-3. Intracellular reactive oxygen species content and mitochondrial membrane potential were analysed by fluorescent probes. The potential mechanisms were explored by molecular biological methods, including Western blotting and quantitative real-time PCR, and were further verified by siRNA interference. Our data showed that ferulic acid significantly inhibited palmitate-induced cell death, rescued mitochondrial membrane potential, reduced reactive oxygen species accumulation, and decreased inflammatory factor activation, including IL-6 and IL-1beta. Ferulic acid significantly stimulated autophagy in hepatocytes, whereas autophagy suppression blocked the protective effect of ferulic acid against lipotoxicity. Ferulic acid-activated autophagy, which was triggered by SIRT1 upregulation, was mechanistically involved in its anti-lipotoxicity effects. SIRT1 silencing blocked most beneficial changes induced by ferulic acid. We demonstrated that the phytochemical ferulic acid, which is found in plant-based food, protected against hepatic lipotoxicity, through the SIRT1/autophagy pathway. Increased intake of ferulic acid-enriched food is a potential strategy to prevent and/or improve metabolic diseases with lipotoxicity as a typical pathological feature.
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影响因子：
21.3
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21.3
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影响因子：
3.4
作者：
Cheng, Chin-Yi;Kao, Shung-Te;Lee, Yu-Chen
通讯作者：
Lee, Yu-Chen
富含γ-谷维素、植物甾醇和阿魏酸的小麦粉可减轻高脂果糖喂养大鼠的脂质和葡萄糖代谢
影响因子：
5.9
作者：
Guo, Xiao-Xuan;Zeng, Zhu;Zhou, Feng
通讯作者：
Zhou, Feng
影响因子：
5.8
作者：
EL-Mesallamy, Hala O.;Gawish, Rania A.;Nada, Ahmed S.
通讯作者：
Nada, Ahmed S.