Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Mol Nutr Food Res. 2017 Dec;61(12). doi: 10.1002/mnfr.201700440. Epub 2017 Oct 26.
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.
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.
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.
正常生理过程需要一个强大的生物计时器，称为生物钟。生物钟节律的失调会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）已被证明具有抗氧化、抗炎和心脏保护的生物活性。本研究旨在探讨生物钟是否参与 EGCG 对胰岛素抵抗的保护作用。
结果表明，EGCG 逆转了氨基葡萄糖诱导的 HepG2 细胞中生物钟基因转录和蛋白表达的相对较浅的昼夜节律波动。EGCG 还通过增强 IRS-1 的酪氨酸磷酸化水平、刺激 GLUT2 的易位以及以 Bmal1 依赖性方式激活 PI3K/AKT 和 AMPK 信号通路，在 HepG2 细胞和原代肝细胞中缓解胰岛素抵抗。氨基葡萄糖刺激的 ROS 过度分泌和线粒体膜电位耗竭在 EGCG 共同处理的 HepG2 细胞中明显减弱，这与线粒体呼吸复合物表达的恢复一致。
结果表明，EGCG 通过增强胰岛素信号和消除氧化应激，具有 Bmal1 依赖性的抗胰岛素抵抗作用，表明 EGCG 可能作为一种有前途的天然营养保健品，用于调节与生物钟相关的代谢紊乱。
