Decrease in myostatin by ladder‐climbing training is associated with insulin resistance in diet‐induced obese rats
Decrease in myostatin by ladder‐climbing training is associated with insulin resistance in diet‐induced obese rats
复制标题
DOI：
10.3760/cma.j.issn.0366-6999.20140022
复制
发表时间：
2014-06
影响因子：
6.1
通讯作者：
L. Tang;Kai Luo;Chen-tao Liu;Xu-dan Wang;Didi Zhang;Aiping Chi;Jing Zhang;Lijun Sun
中科院分区：
文献类型：
--
作者：
L. Tang;Kai Luo;Chen-tao Liu;Xu-dan Wang;Didi Zhang;Aiping Chi;Jing Zhang;Lijun Sun
背景 肌肉生长抑制素 (MSTN) 的抑制与骨骼肌萎缩和胰岛素抵抗 (IR) 相关。然而，很少有研究将爬梯训练 (LCT) 和 IR 抑制 MSTN 联系起来。因此，我们打算确定LCT与IR之间的相关性，并分析LCT抑制MSTN调节IR的信号通路。方法将大鼠随机分配至两种饮食：正常颗粒饮食（NPD，n=8）和高脂饮食（HFD，n=16）。 8周后，HFD大鼠被随机重新分配到两组（每组n = 8）：HFD久坐训练（HFD-S）和高脂饮食爬梯训练（HFD-LCT）。 HFD-LCT 大鼠被分配至 LCT 组，为期 8 周。使用蛋白质印迹、免疫组织化学和酶测定来测量 MSTN、GLUT4、PI3K、Akt 和 Akt 激活靶标（mTOR、FoxO1 和 GSK-3）的表达水平和活性。结果 LCT 显着改善 HDF 喂养大鼠的 IR 和全身胰岛素敏感性。 LCT后肥胖大鼠的匹配血清（42%，P=0.007）和肌肉样本（25%，P=0.035）中MSTN蛋白水平下降，其受体mRNA表达也下降（16%，P=0.041）。但LCT组胰岛素受体mRNA表达量与NPD组和HFD-S组相比无明显变化（P=0.074）。爬梯训练显着增强高脂饮食大鼠的 PI3K 活性（1.7 倍，P=0.024）和 Akt 磷酸化（83.3%，P=0.022），显着增加 GLUT4 蛋白表达（84.5%，P=0.036），增强 mTOR 磷酸化（4.8 倍，P <0.001）并抑制 FoxO1 磷酸化(57.7%, P=0.020)，但不影响GSK-3的磷酸化。结论 LCT 显着降低饮食诱导的肥胖大鼠的 IR。在 HFD 喂养的大鼠中，MSTN 可能通过 LCT 通过 PI3K/Akt/mTOR 和 PI3K/Akt/FoxO1 信号通路调节 IR 和脂肪积累发挥重要作用。
Background Suppression of myostatin (MSTN) has been associated with skeletal muscle atrophy and insulin resistance (IR). However, few studies link MSTN suppression by ladder‐climbing training (LCT) and IR. Therefore, we intended to identify the correlation with IR between LCT and to analyze the signaling pathways through which MSTN suppression by LCT regulates IR. Methods The rats were randomly assigned to two types of diet: normal pellet diet (NPD, n=8) and high‐fat diet (HFD, n=16). After 8 weeks, the HFD rats were randomly re‐assigned to two groups (n=8 for each group): HFD sedentary (HFD‐S) and high‐fat diet ladder‐climbing training (HFD‐LCT). HFD‐LCT rats were assigned to LCT for 8 weeks. Western blotting, immunohistochemistry and enzyme assays were used to measure expression levels and activities of MSTN, GLUT4, PI3K, Akt and Akt‐activated targets (mTOR, FoxO1 and GSK‐3). Results The LCT significantly improved IR and whole‐body insulin sensitivity in HDF‐fed rats. MSTN protein levels decreased in matching serum (42%, P=0.007) and muscle samples (25%, P=0.035) and its receptor mRNA expression also decreased (16%, P=0.041) from obese rats after LCT. But the mRNA expression of insulin receptor had no obvious changes in LCT group compared with NPD and HFD‐S groups (P=0.074). The ladder‐climbing training significantly enhanced PI3K activity (1.7‐fold, P=0.024) and Akt phosphorylation (83.3%, P=0.022) in HFD‐fed rats, significantly increased GLUT4 protein expression (84.5%, P=0.036), enhanced phosphorylation of mTOR (4.8‐fold, P <0.001) and inhibited phosphorylation of FoxO1 (57.7%, P=0.020), but did not affect the phosphorylation of GSK‐3. Conclusions The LCT significantly reduced IR in diet‐induced obese rats. MSTN may play an important role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and PI3K/Akt/FoxO1 signaling pathway in HFD‐fed rats.