Activation of adiponectin receptors has negative impact on muscle mass in C2C12 myotubes and fast-type mouse skeletal muscle.

Activation of adiponectin receptors has negative impact on muscle mass in C2C12 myotubes and fast-type mouse skeletal muscle.
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DOI:
10.1371/journal.pone.0205645
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Goto K
Goto K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ito R;Higa M;Goto A;Aoshima M;Ikuta A;Ohashi K;Yokoyama S;Ohno Y;Egawa T;Miyata H;Goto K

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本研究研究了 AdipoRon(脂联素受体 1 (AdipoR1) 和 AdipoR2 的激动剂)对 C57BL/6J 小鼠 C2C12 细胞的蛋白质含量、肌管直径、每个肌管的核数以及骨骼肌质量的影响。 AdipoRon 以剂量依赖性方式抑制 C2C12 细胞 C2C12 肌管的蛋白质含量、肌管直径和每个肌管的细胞核数量。 C2C12 肌管中与脂联素相关的蛋白质含量、直径和每个肌管细胞核数量的下降可通过敲低 AdipoR1 和/或 AdipoR2 部分得到缓解。 AMPK 的磷酸化水平显示出 AdipoRon 增加的趋势。在 20 μM AdipoRon 下观察到 AMPK 磷酸化水平显着增加。 AdipoR1 和/或 AdipoR2 的敲低可挽救 AdipoRon 相关的 C2C12 肌管蛋白质含量下降。 C2C12 肌管中与 AdipoRon 相关的 AMPK 磷酸化水平的增加可通过敲低 AdipoR1 和/或 AdipoR2 来抑制。向小鼠连续静脉注射 AdipoRon 导致跖肌 (PLA) 湿重下降,但比目鱼肌 (SOL) 却没有下降。 AdipoRon 给药显着降低了 PLA(而非 SOL)的平均纤维横截面积。一方面,AdipoRon 给药上调了 SOL 和 PLA 肌肉中磷酸化 AMPK 和泛素化蛋白的表达水平。另一方面,AdipoRon 给药并未引起 SOL 和 PLA 肌肉中嘌呤霉素标记蛋白的表达水平发生变化。趾长伸肌 (EDL) 中脂联素的表达水平随着年龄的增长而增加,但 SOL 肌肉中的脂联素表达水平却没有增加。衰老对两种肌肉中 AdipoR1 和 AdipoR2 的表达水平没有影响。 EDL 中 AMPK 的磷酸化水平会随着年龄的增长而增加,但 SOL 肌肉中的磷酸化水平不会增加。这项研究的结果表明,高水平的循环脂联素可能会导致骨骼肌萎缩,尤其是快速型肌肉。
This study investigated the effects of AdipoRon, which is an agonist for adiponectin receptor 1 (AdipoR1) and AdipoR2, on the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells and skeletal muscle mass in C57BL/6J mice. AdipoRon suppressed the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells of C2C12 myotubes in a dose-dependent manner. Adiponectin-associated decline of protein content, diameter, and number of nuclei per myotube in C2C12 myotubes was partially rescued by knockdown of AdipoR1 and/or AdipoR2. Phosphorylation level of AMPK showed a trend to be increased by AdipoRon. A significant increase in phosphorylation level of AMPK was observed at 20 μM AdipoRon. Knockdown of AdipoR1 and/or AdipoR2 rescued AdipoRon-associated decrease in protein content of C2C12 myotubes. AdipoRon-associated increase in phosphorylation level of AMPK in C2C12 myotubes was suppressed by knockdown of AdipoR1 and/or AdipoR2. Successive intravenous injections of AdipoRon into mice caused a decrease in the wet weight of plantaris muscle (PLA), but not in soleus muscle (SOL). Mean fiber cross-sectional area of PLA, but not of SOL, was significantly decreased by AdipoRon administration. On the one hand, the expression level of phosphorylated AMPK and ubiquitinated protein in SOL and PLA muscles was upregulated by AdipoRon administration. On the other hand, AdipoRon administration induced no changes in the expression level of puromycin-labeled proteins in both SOL and PLA muscles. Expression level of adiponectin in extensor digitorum longus (EDL) muscle was increased by aging, but not in SOL muscle. Aging had no effect on the expression level of AdipoR1 and AdipoR2 in both muscles. Phosphorylation level of AMPK in EDL was increased by aging, but not SOL muscle. Results from this study suggest that high level of circulating adiponectin may induce skeletal muscle atrophy, especially fast-type muscle.
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