Epigallocatechin-3-gallate suppresses differentiation of adipocytes via regulating the phosphorylation of FOXO1 mediated by PI3K-AKT signaling in 3T3-L1 cells.
Epigallocatechin-3-gallate suppresses differentiation of adipocytes via regulating the phosphorylation of FOXO1 mediated by PI3K-AKT signaling in 3T3-L1 cells.
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表没食子儿茶素-3-没食子酸酯通过调节 3T3-L1 细胞中 PI3K-AKT 信号介导的 FOXO1 磷酸化来抑制脂肪细胞分化
DOI：
10.18632/oncotarget.23590
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发表时间：
2018-01-26
期刊：
影响因子：
--
通讯作者：
Huang Q
中科院分区：
文献类型：
--
作者：
Lu Y;Chen J;Xian T;Zhou Y;Yuan W;Wang M;Gan Y;Wang K;Xiong S;Ma C;Yu X;Huang Q
表没食子儿茶素没食子酸酯（Epigallocatechin-3-gallate，EGCG）是绿色茶的重要有效成分。已知EGCG具有抗氧化、抗血管生成、抗肿瘤、心血管保护和调节血脂等功能。FOXO 1是蛋白激酶B（AKT）的下游信号之一，参与脂肪的形成。本研究旨在探讨表没食子儿茶素没食子酸酯（EGCG）对脂肪分化的影响及其可能机制。3 T3-L1细胞分别用MTT法诱导2、4、6和8天。在诱导期间，细胞用EGCG（5 μM、10 μM、50 μM和100 μM）或DMSO处理前2天。此外，另一批3 T3-L1细胞用SC-3036（PI 3 K激活剂，10 μM）或LY 294002（PI 3 K抑制剂，10 μM）单独或与EGCG（100 μM）组合处理指定时间。分别检测中糖浓度、血脂水平、TNF-α、脂联素、瘦素水平以及FOXO 1、磷酸化FOXO 1（P-FOXO 1）、过氧化物酶体增殖物激活受体γ（PPARγ）、脂肪酸合成酶（FAS）的表达。本研究表明，EGCG以浓度依赖性方式抑制脂肪形成过程中的葡萄糖摄取、脂质积累和脂肪因子分泌，这表明EGCG抑制脂肪细胞的分化、成熟和功能。此外，EGCG还下调了PPARγ和P-FOXO 1的表达水平。PI 3 K激活剂可逆转EGCG引起的上述变化，提示EGCG的抑制作用可能通过PI 3 K-AKT-FOXO 1通路负性调节PPARγ的表达。本研究结果为EGCG防治肥胖相关疾病提供了坚实的基础。
Epigallocatechin-3-gallate (EGCG) is a pivotal effective component of green tea. It is known that EGCG has antioxidant activity, anti-angiogenesis, anti-tumor, cardiovascular protection and blood lipid regulation functions. Forkhead box-O1 (FOXO1) is one of the downstream signals of protein kinase B (AKT) and takes part in adipogenesis. The purpose of this study is to investigate the effects of EGCG on adipose differentiation and the likely mechanisms. 3T3-L1 cells were induced by DMI for 2, 4, 6 and 8 days, respectively. During induction, the cells were treated with EGCG (5 μM, 10 μM, 50 μM and 100 μM) or DMSO for the first 2 days. In addition, another batch of 3T3-L1cells were treated with SC-3036 (PI3K activator, 10 µM), or LY294002 (PI3K inhibitor, 10 µM) alone or combined with EGCG (100 μM) for the indicated times. Medium glucose concentration, lipid accumulation, the levels of TNF-α, resistin, adiponectin and leptin and the expression of FOXO1, phosphorylated-FOXO1 (P-FOXO1), PPARγ, fatty acid synthase (FAS) were detected, respectively. The present study demonstrated that EGCG inhibited glucose uptake, lipid accumulation and adipokine secretion in a concentration-dependent manner during adipogenesis, which suggests that EGCG inhibits adipocyte’s differentiation, maturation and functions. Moreover, EGCG also down-regulated the expression levels of PPARγ and P-FOXO1. Conversely, the PI3K activator reversed these changes caused by EGCG, suggesting that the inhibitory effects of EGCG may be mediated by PI3K-AKT-FOXO1 pathway to negatively regulate the expression of PPARγ. The findings will provide a solid foundation for EGCG to prevent and cure the obesity-associated diseases.