Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition.
Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition.
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DOI：
10.1038/srep39825
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发表时间：
2017-01-04
影响因子：
4.6
通讯作者：
Shimomura Y
中科院分区：
文献类型：
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作者：
Ishikawa T;Kitaura Y;Kadota Y;Morishita Y;Ota M;Yamanaka F;Xu M;Ikawa M;Inoue N;Kawano F;Nakai N;Murakami T;Miura S;Hatazawa Y;Kamei Y;Shimomura Y
支链氨基酸（BCAA）是哺乳动物必需的氨基酸，在蛋白质代谢的调节中发挥着关键作用。然而，BCAA缺乏对体内骨骼肌蛋白质代谢的影响仍不清楚。在这里，我们通过专门加速骨骼肌和心脏中的 BCAA 分解代谢来产生具有较低 BCAA 浓度的小鼠（BDK-mKO 小鼠）。当喂食富含蛋白质的食物时，这些小鼠看起来很健康，没有任何明显的缺陷；然而，一次性摄入支链氨基酸表明，与相应的对照小鼠相比，BDK-mKO 小鼠骨骼肌中的 mTORC1 敏感性增强。当给这些小鼠喂食低蛋白饮食时，肌原纤维蛋白的浓度显着降低（但可溶性蛋白除外），并且 mTORC1 活性降低，但自噬没有显着变化。在饮用水中添加 BCAA 可减轻肌原纤维蛋白水平和 mTORC1 活性的下降。这些结果表明，BCAA 通过保持 mTORC1 活性而不是通过抑制自噬和翻译，在蛋白质营养不良期间维持肌原纤维蛋白至关重要。这是第一份揭示支链氨基酸对体内骨骼肌蛋白质代谢重要性的报告。
Branched-chain amino acids (BCAAs) are essential amino acids for mammals and play key roles in the regulation of protein metabolism. However, the effect of BCAA deficiency on protein metabolism in skeletal muscle in vivo remains unclear. Here we generated mice with lower BCAA concentrations by specifically accelerating BCAA catabolism in skeletal muscle and heart (BDK-mKO mice). The mice appeared to be healthy without any obvious defects when fed a protein-rich diet; however, bolus ingestion of BCAAs showed that mTORC1 sensitivity in skeletal muscle was enhanced in BDK-mKO mice compared to the corresponding control mice. When these mice were fed a low protein diet, the concentration of myofibrillar protein was significantly decreased (but not soluble protein) and mTORC1 activity was reduced without significant change in autophagy. BCAA supplementation in drinking water attenuated the decreases in myofibrillar protein levels and mTORC1 activity. These results suggest that BCAAs are essential for maintaining myofibrillar proteins during protein undernutrition by keeping mTORC1 activity rather than by inhibiting autophagy and translation. This is the first report to reveal the importance of BCAAs for protein metabolism of skeletal muscle in vivo.