(-)-Epigallocatechin-3-gallate Ameliorates Insulin Resistance and Mitochondrial Dysfunction in HepG2 Cells: Involvement of Bmal1
(-)-Epigallocatechin-3-gallate Ameliorates Insulin Resistance and Mitochondrial Dysfunction in HepG2 Cells: Involvement of Bmal1
复制标题
(-)-表没食子儿茶素-3-没食子酸酯改善 HepG2 细胞的胰岛素抵抗和线粒体功能障碍：Bmal1 的参与
DOI：
10.1002/mnfr.201700440
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发表时间：
2017-12-01
影响因子：
5.2
通讯作者：
Liu, Xuebo
中科院分区：
文献类型：
--
作者：
Mi, Yashi;Qi, Guoyuan;Liu, Xuebo
范围正常的生理过程需要一个强大的生物计时器称为昼夜节律钟。昼夜节律失调导致多种代谢综合征，包括肥胖和胰岛素抵抗。表没食子儿茶素没食子酸酯（EGCG）具有抗氧化、抗炎和保护心脏的生物活性。本研究的目的是探讨是否昼夜节律钟参与EGCG对insulinresistance.Methods和结果的保护作用。结果表明，EGCG逆转相对较浅的昼夜节律钟基因的转录和蛋白表达的每日振荡诱导葡糖胺在HepG 2细胞。EGCG还通过增强IRS-1的酪氨酸磷酸化水平、刺激GLUT 2的易位、以及以Bmal 1依赖性方式激活HepG 2细胞和原代肝细胞中的PI 3 K/AKT以及AMPK信号通路来减轻胰岛素抵抗。结论EGCG通过增强胰岛素信号通路和消除氧化应激，具有Bmal 1依赖性的抗胰岛素抵抗作用。提示EGCG可用作调节与生物钟相关的代谢紊乱的有前景的天然营养药。
Scope Normal physiological processes require a robust biological timer called the circadian clock. Dysregulation of circadian rhythms contributes to a variety of metabolic syndrome, including obesity and insulin resistance. (-)-Epigallocatechin-3-gallate (EGCG) has been demonstrated to possess antioxidant, anti-inflammatory, and cardioprotective bioactivities. The objective of this study was to explore whether the circadian clock is involved in the protective effect of EGCG against insulin resistance.Methods and results The results demonstrated that EGCG reverses the relatively shallow daily oscillations of circadian clock genes transcription and protein expression induced by glucosamine in HepG2 cells. EGCG also alleviates insulin resistance by enhancing tyrosine phosphorylated levels of IRS-1, stimulating the translocation of GLUT2, and activating PI3K/AKT as well as AMPK signaling pathways in a Bmal1-dependent manner both in HepG2 cells and primary hepatocytes. Glucosamine-stimulated excessive secretions of ROS and depletions of mitochondrial membrane potential were notably attenuated in EGCG co-treated HepG2 cells, which consistent with the recovery in expression of mitochondrial respiration complexes.Conclusion The results demonstrated that EGCG possesses a Bmal1-dependent efficacy against insulin resistance conditions by strengthening the insulin signaling and eliminating oxidative stress, suggesting that EGCG may serve as a promising natural nutraceutical for the regulation of metabolic disorders relevant to circadian clocks.