Resveratrol induces cell apoptosis in adipocytes via AMPK activation
Resveratrol induces cell apoptosis in adipocytes via AMPK activation
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DOI：
10.1016/j.bbrc.2015.01.034
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发表时间：
2015-02-20
影响因子：
3.1
通讯作者：
Zhu, Wei
中科院分区：
文献类型：
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作者：
Chen, Sifan;Zhou, Niman;Zhu, Wei
白藜芦醇是一种多酚类化合物，具有抗炎、抗氧化、抗胰岛素抵抗等特性。此外，白藜芦醇在多种癌细胞系中发挥促凋亡作用。然而，白藜芦醇对脂肪细胞凋亡的调节作用和机制仍很不清楚。在本研究中，我们发现白藜芦醇处理可以诱导小鼠3T3-L1脂肪细胞的凋亡。此外，白藜芦醇通过线粒体膜电位的降低和caspase 3的激活激活了线粒体的凋亡信号通路。从机制上，我们发现当白藜芦醇作用于细胞时，AMP激活的蛋白激酶α(AMPKα)的磷酸化水平升高，同时蛋白激酶B(AKT)的磷酸化水平降低。通过使用AMPKα的小干扰RNA和p-AKT的特异性抑制剂，发现AMPKα的激活可以抑制p-AKT下游，从而激活线粒体介导的细胞凋亡途径。此外，我们还观察到Res对小鼠原代脂肪细胞具有类似的促凋亡作用。我们的发现阐明了白藜芦醇对脂肪细胞的凋亡作用和潜在的机制，表明白藜芦醇在治疗或预防肥胖和相关代谢症状方面具有潜在的治疗应用。(C)2015 Elsevier Inc.保留所有权利。
Resveratrol is identified as polyphenolic compound with anti-inflammatory, antioxidant, anti-insulin resistance characteristics. Moreover, resveratrol exerts pro-apoptotic effects in varieties of cancer cell lines. However, effects and mechanisms of resveratrol on the regulation of adipocytes apoptosis remain largely unknown. In this study, we found that resveratrol treatment could induce cell apoptosis in murine 3T3-L1 adipocytes. Furthermore, resveratrol activated the mitochondrial apoptotic signaling pathway with the decrease in the mitochondrial membrane potential (MMP), and the activation of caspase 3. Mechanistically, we found that phosphorylation level of AMP-activated protein kinase alpha (AMPK alpha) was elevated, accompany with reduced level of phosphorylation of protein kinase B (AKT) when cells were exposed to resveratrol. By using small interfering RNAs of AMPK alpha and specific inhibitor for p-AKT, it was shown that activation of AMPK alpha could inhibit downstream of p-AKT, consequently activating mitochondrion-mediated apoptotic pathway. Additionally, we observed similar pro-apoptotic effects of Res on mouse primary adipocytes. Our findings clarified the apoptotic effects and underlying mechanisms of resveratrol in adipocytes, suggesting its potential therapeutic application in the treatment or prevention of obesity and related metabolic symptoms. (C) 2015 Elsevier Inc. All rights reserved.