Flavonoid derivative (Fla-CN) inhibited adipocyte differentiation via activating AMPK and up-regulating microRNA-27 in 3T3-L1 cells
Flavonoid derivative (Fla-CN) inhibited adipocyte differentiation via activating AMPK and up-regulating microRNA-27 in 3T3-L1 cells
复制标题
类黄酮衍生物 (Fla-CN) 通过激活 AMPK 和上调 3T3-L1 细胞中的 microRNA-27 抑制脂肪细胞分化
DOI：
10.1016/j.ejphar.2017.01.009
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发表时间：
2017-02-15
影响因子：
5
通讯作者：
Duan, Hong-Quan
中科院分区：
文献类型：
--
作者：
Gan, Chun-Chun;Ni, Tian-Wen;Duan, Hong-Quan
Fla-CN (3-O-[（E)-4-(4- cyanphenyl)-2-oxobut-3-en-l-yl]山奈酚）是一种半合成的类黄酮衍生物，在体内具有抗糖尿病作用。我们之前的研究揭示了Fla-CN在体内抗肥胖和抗糖尿病中的作用，但其潜在的机制仍有待研究。本研究旨在探讨体外抗脂肪生成的机制。Fla-CN显著抑制细胞内脂质积累，且呈剂量依赖性，其体外抑制作用主要局限于脂肪细胞分化早期。进一步的研究发现，Fla-CN上调miR-27a/b的表达水平，并抑制其靶基因的表达，包括过氧化物酶体增殖物激活受体γ (PPAR γ)和CCAAT/增强子结合蛋白a （C/EBP α）。此外，在脂肪细胞前分化过程中，Fla-CN也增强了amp活化蛋白激酶（AMPK）的磷酸化。当细胞被miR-27a/b抑制剂和AMPK抑制剂化合物c处理时，这些作用被消除。此外，Fla-CN降低了脂肪细胞特异性基因的表达，如固醇调节元件结合转录因子1c （SREBP-1c）、脂肪酸合成酶（FAS）和脂肪细胞脂肪酸结合蛋白（aP2）。综上所述，这些结果提示了Fla-CN通过miR-27a/b诱导和AMPK激活抑制3T3-L1细胞脂肪细胞分化的机制。
Fla-CN (3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-l-yl] kaempferol) is a semi-synthesized flavonoid derivative of tiliroside which exhibited anti-diabetic effect in vivo. Our previous study revealed the role of Fla-CN in anti-obesity and anti-diabetes in vivo, but the underlying mechanism remained to be addressed. The present study aimed to investigate the mechanism of anti-adipogenesis in vitro. Fla-CN markedly inhibited intracellular lipid accumulation in a dose-dependent manner, and the inhibitory effect was mainly limited to the early stage of adipocyte differentiation in vitro. Further investigations revealed that Fla-CN up-regulated the expression level of miR-27a/b and suppressed its target genes expression including peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein a (C/EBP alpha). Furthermore, the phosphorylation of AMP-activated protein kinase (AMPK) was also enhanced by Fla-CN in pre-adipocyte differentiation. These effects were abolished when cells were treated with miR-27a/b inhibitor and AMPK inhibitor Compound C. Additionally, Fla-CN reduced the expressions of adipocyte-specific genes such as sterol regulatory element binding transcription factor 1c (SREBP-1c), fatty acid synthase (FAS) and adipocyte fatty acid binding protein (aP2). In conclusion, these results suggested a mechanism of Fla-CN for adipocyte differentiation inhibition of 3T3-L1 cells through miR-27a/b induction and AMPK activation.