(-)-Epigallocatechin-3-O-gallate at a high concentration may induce lipolysis via ATP consumption by activation of stress defense mechanisms
(-)-Epigallocatechin-3-O-gallate at a high concentration may induce lipolysis via ATP consumption by activation of stress defense mechanisms
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DOI：
10.1093/bbb/zbaa056
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发表时间：
2021-02-18
影响因子：
1.6
通讯作者：
Murakami，Akira
中科院分区：
文献类型：
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作者：
Suihara，Satoki;Ishisaka，Akari;Murakami，Akira
迄今为止，绿色茶儿茶素已在各种实验模型中被证明具有抗肥胖作用。然而，触发这些现象的上游分子事件仍有待确定。在这项研究中，我们发现（−）-表没食子儿茶素-3-O-没食子酸酯（EGCG）促进脂质负载的Huh 7人肝癌细胞中的脂解。值得注意的是，高浓度的EGCG诱导氧化应激和蛋白质应激（蛋白质应激），导致应激防御机制的激活，例如抗氧化剂和2相解毒酶以及热休克蛋白的mRNA表达。此外，EGCG降低了细胞内ATP水平，而从培养基中摄取葡萄糖可能是为了能量平衡。EGCG还上调脂肪甘油三酯脂肪酶的表达，并激活AMP激活的蛋白激酶。总的来说，这些结果表明，表没食子儿茶素没食子酸酯诱导脂解，以补偿ATP减少来自激活应激防御系统对它的氧化和蛋白质应激特性。
Green tea catechins have thus far been demonstrated to have antiobesity effects in a variety of experimental models. However, upstream molecular events triggering those phenomena remain to be identified. In this study, we found that (−)-epigallocatechin-3-O-gallate (EGCG) promoted lipolysis in lipid-loaded Huh7 human hepatoma cells. Notably, EGCG at a high concentration induced both oxidative stress and protein stress (proteo-stress), leading to activation of stress defense mechanisms, such as mRNA expressions of antioxidant and phase-2 detoxifying enzymes, and heat shock proteins. Furthermore, EGCG decreased the level of intracellular ATP, while glucose uptake from culture media was promoted possibly for energy homeostasis. EGCG also upregulated the expression of adipose triglyceride lipase, and activated AMP-activated protein kinase. Collectively, these results suggest that EGCG induces lipolysis to compensate for ATP reduction derived from activation of stress defense systems against its oxidative and proteo-stress properties.