Nebivolol stimulates mitochondrial biogenesis in 3T3-L1 adipocytes
Nebivolol stimulates mitochondrial biogenesis in 3T3-L1 adipocytes
复制标题
Nebivolol 刺激 3T3-L1 脂肪细胞中的线粒体生物合成。
DOI：
10.1016/j.bbrc.2013.07.055
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发表时间：
2013-08-16
影响因子：
3.1
通讯作者：
Shen, Weili
中科院分区：
文献类型：
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作者：
Huang, Chenglin;Chen, Dongrui;Shen, Weili
奈必洛尔是第三代β-肾上腺素能受体（β-AR）阻滞剂，具有额外的有益作用，包括改善肥胖患者的脂质和葡萄糖代谢。然而，奈必洛尔在调节血脂方面的作用的潜在机制在很大程度上仍然未知。在这项研究中，我们研究了奈必洛尔在3 T3-L1脂肪细胞线粒体生物合成中的作用。将3 T3-L1细胞暴露于奈必洛尔24 h可增加线粒体DNA拷贝数、线粒体蛋白水平和参与线粒体生物发生的转录因子的表达，包括PPAR-gamma辅激活因子-1 α（PGC-1 α）、Sirtuin 3（Sirt 3）、线粒体转录因子A（Tfam）和核相关因子1（Nrf 1）。这些变化伴随着耗氧量的增加和3 T3-L1脂肪细胞中脂肪酸氧化和抗氧化酶的基因表达的增加，包括奈必洛尔诱导的内皮型一氧化氮合酶（eNOS），以及环磷酸鸟苷（cGMP）形成的增加。用NG-硝基-L-精氨酸甲酯（I-NAME）预处理减弱奈必洛尔诱导的线粒体生物合成，可溶性鸟苷酸环化酶抑制剂ODQ也是如此。与奈必洛尔单独治疗相比，奈必洛尔和β 3-AR阻断剂SR 59230 A治疗显著降低了PGC-1 α、Sirt 3和锰超氧化物歧化酶（MnSOD）蛋白水平。这些数据表明，奈必洛尔促进的脂肪细胞线粒体合成和代谢主要通过eNOS/cGMP依赖性途径介导，并由β 3-AR受体激活启动。(C)2013 Elsevier Inc. All rights reserved.
Nebivolol is a third-generation beta-adrenergic receptor (beta-AR) blocker with additional beneficial effects, including the improvement of lipid and glucose metabolism in obese individuals. However, the underlying mechanism of nebivolol's role in regulating the lipid profile remains largely unknown. In this study, we investigated the role of nebivolol in mitochondrial biogenesis in 3T3-L1 adipocytes. Exposure of 3T3-L1 cells to nebivolol for 24 h increased mitochondrial DNA copy number, mitochondrial protein levels and the expression of transcription factors involved in mitochondrial biogenesis, including PPAR-gamma coactivator-1 alpha (PGC-1 alpha), Sirtuin 3 (Sirt3), mitochondrial transcription factor A (Tfam) and nuclear related factor 1 (Nrf1). These changes were accompanied by an increase in oxygen consumption and in the expression of genes involved in fatty acid oxidation and antioxidant enzymes in 3T3-L1 adipocytes, including nebivolol-induced endothelial nitric oxide synthase (eNOS), as well as an increase in the formation of cyclic guanosine monophosphate (cGMP). Pretreatment with NG-nitro-L-arginine methyl ester (I-NAME) attenuated nebivolol-induced mitochondrial biogenesis, as did the soluble guanylate cyclase inhibitor, ODQ. Treatment with nebivolol and beta 3-AR blocker SR59230A markedly attenuated PGC-1 alpha, Sirt3 and manganese superoxide dismutase (MnSOD) protein levels in comparison to treatment with nebivolol alone. These data indicate that the mitochondrial synthesis and metabolism in adipocytes that is promoted by nebivolol is primarily mediated through the eNOS/cGMP-dependent pathway and is initiated by the activation of beta 3-AR receptors. (C) 2013 Elsevier Inc. All rights reserved.