| 张雨点,谢锦艳,李小川,张志杰,李 珍.木犀草素是具有PPARγ激动剂活性的新型AMPK激活剂[J].现代生物医学进展英文版,2019,19(9):1601-1607. |
| 木犀草素是具有PPARγ激动剂活性的新型AMPK激活剂 |
| Luteolin is a Novel AMPK Activator with Partial PPARγ Agonist Activity |
| Received:July 28, 2018 Revised:August 23, 2018 |
| DOI：10.13241/j.cnki.pmb.2019.09.001 |
| 中文关键词: 木犀草素 PPARγ AMPK 脂联素 胰岛素敏感性 |
| 英文关键词: Luteolin PPARγ AMPK Adiponectin Insulin Sensitivity |
| 基金项目:国家自然科学基金项目（31570760） |
| Author Name | Affiliation | E-mail | | ZHANG Yu-dian | MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, 100084, China | yudian_zhang@163.com | | XIE Jin-yan | Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China | | | LI Xiao-chuan | MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, 100084, China | | | ZHANG Zhi-jie | Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China | | | LI Zhen | MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, 100084, China | |
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| 中文摘要: |
| 摘要 目的：木犀草素是一种天然黄酮类化合物，早期报导其能激活PPARγ，本实验室发现其也能激活AMPK。因此本研究验证木犀草素在脂肪细胞中能否激活PPARγ和AMPK，并探究这两种活性对脂肪前体细胞分化及脂联素高聚化的影响。方法：使用LanthaScreen TR-FRET PPARγ竞争性结合检测试剂盒检测木犀草素与PPARγ的结合能力，并用PPRE转录激活报告基因体系验证木犀草素是否激活PPARγ转录活性，利用油红O染色法检测木犀草素对3T3-L1脂肪前体细胞分化的影响，采用RNA干扰沉默成熟脂肪细胞中AMPKα1，用Western Blot检测相关蛋白水平。结果：木犀草素能直接结合PPARγ，其IC50为1880 nmoL?L-1，并显示剂量依赖的PPARγ转录激活活性，抑制PPARγ Ser-273位点磷酸化。木犀草素能升高pAMPK（Thr-172）水平，抑制脂肪前体细胞分化，升高脂联素高聚化水平。结论：木犀草素通过激活AMPK和PPARγ调控脂肪前体细胞分化和脂联素高聚化，是一种具有PPARγ激动剂活性的新AMPK激活剂，有望成为治疗Ⅱ型糖尿病和肥胖等代谢紊乱疾病的潜在药物。 |
| 英文摘要: |
| ABSTRACT Objective: In this study, we reported that luteolin, a natural flavonoid with partial PPARγ-agonist activity, also acti- vates AMPK, and investigated the effects of luteolin on preadipocytes differentiation and adiponectin multimerization in adipocytes. Methods: In vitro binding of luteolin to PPARγ was analyzed by a LanthaScreen time-resolved fluorescent energy transfer (TR-FRET) PPARγ competitive binding assay; the effect of luteolin on the transcriptional activity of PPARγ was examined by luciferase reporter assays; the effect of luteolin on preadipocytes differentiation was examined by Oil Red O staining; mature 3T3-L1 adipocytes transfected with mouse AMPKα1 siRNA were treated with luteolin to detect the levels of total adiponectin and adiponectin oligomers. Results: The competitive binding assay confirmed direct binding of luteolin to the LBD of PPARγ with IC50 being 1880 nmoL?L-1. Luteolin dose-de- pendently increased the transcriptional activity of PPARγ and inhibited the phosphorylation of PPARγ at Ser-273. Luteolin increased the level of pAMPK(Thr-172), inhibited preadipocytes differentiation, and increased the level of high molecular weight adiponectin (HMW). Conclusion: Luteolin is a novel AMPK activator with partial PPARγ agonist activity. Luteolin inhibits preadipocytes differen- tiation and promotes multimerization of adiponectin by activating both AMPK and PPARγ. The dual-activity makes luteolin a potential insulin sensitizer for the treatment of type II diabetes. |
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