Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.
Food Funct. 2018 Mar 1;9(3):1510-1523. doi: 10.1039/c7fo01554b. Epub 2018 Feb 9.
As a major nutraceutical component of green tea (-)-epigallocatechin-3-gallate (EGCG) has attracted interest from scientists due to its well-documented antioxidant and antiobesity bioactivities. In the current study, we aimed to investigate the protective effect of EGCG on metabolic misalignment and in balancing the redox status in mice liver and HepG2 cells under insulin resistance condition. Our results indicated that EGCG accelerates the glucose uptake and evokes IRS-1/Akt/GLUT2 signaling pathway via dampening the expression of protein tyrosine phosphatase 1B (PTP1B). Consistently, ectopic expression of PTP1B by Ad-PTP1B substantially impaired EGCG-elicited IRS-1/Akt/GLUT2 signaling pathway. Moreover, EGCG co-treatment stimulated nuclear translocation of Nrf2 by provoking P13K/AKT signaling pathway and thus modulated the downstream expressions of antioxidant enzymes such as HO-1 and NQO-1 in HepG2 cells. Furthermore, knockdown Nrf2 by small interfering RNA (siRNA) notably enhanced the expression of PTP1B and blunt EGCG-stimulated glucose uptake. Consistent with these results, in vivo study revealed that EGCG supplement significantly ameliorated high-fat and high-fructose diet (HFFD)-triggered insulin resistance and oxidative stress by up-regulating the IRS-1/AKT and Keap1/Nrf2 transcriptional pathways. Administration of an appropriate chemopreventive agent, such as EGCG, could potentially serve as an additional therapeutic intervention in the arsenal against obesity.
作为绿茶的一种主要营养成分，(-)-表没食子儿茶素没食子酸酯（EGCG）由于其具有良好的抗氧化和抗肥胖生物活性，引起了科学家的兴趣。在本研究中，我们旨在研究 EGCG 在胰岛素抵抗条件下对代谢失稳的保护作用，并平衡小鼠肝脏和 HepG2 细胞中的氧化还原状态。我们的结果表明，EGCG 通过抑制蛋白酪氨酸磷酸酶 1B（PTP1B）的表达来加速葡萄糖摄取，并激活 IRS-1/Akt/GLUT2 信号通路。一致地，Ad-PTP1B 异位表达显著削弱了 EGCG 诱导的 IRS-1/Akt/GLUT2 信号通路。此外，EGCG 共同处理通过刺激 P13K/AKT 信号通路刺激核易位的 Nrf2，从而调节 HepG2 细胞中抗氧化酶如 HO-1 和 NQO-1 的下游表达。此外，小干扰 RNA（siRNA）敲低 Nrf2 显著增强了 PTP1B 的表达，并削弱了 EGCG 刺激的葡萄糖摄取。与这些结果一致，体内研究表明，EGCG 补充剂通过上调 IRS-1/AKT 和 Keap1/Nrf2 转录途径，显著改善了高脂肪和高果糖饮食（HFFD）引起的胰岛素抵抗和氧化应激。施用适当的化学预防剂，如 EGCG，可能成为肥胖症治疗的另一种治疗干预手段。
