Essential Amino Acid-Enriched Diet Alleviates Dexamethasone-Induced Loss of Muscle Mass and Function through Stimulation of Myofibrillar Protein Synthesis and Improves Glucose Metabolism in Mice.

Essential Amino Acid-Enriched Diet Alleviates Dexamethasone-Induced Loss of Muscle Mass and Function through Stimulation of Myofibrillar Protein Synthesis and Improves Glucose Metabolism in Mice.
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DOI:
10.3390/metabo12010084
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发表时间:
2022-01-16
期刊:
影响因子:
4.1
通讯作者:
Kim IY
Kim IY
中科院分区:
生物学3区
文献类型:
--
作者:
Kim Y;Park S;Lee J;Jang J;Jung J;Koh JH;Choi CS;Wolfe RR;Kim IY

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地塞米松 (DEX) 会引起蛋白质周转失调,导致肌肉萎缩和葡萄糖代谢受损。膳食必需氨基酸 (EAA) 可以诱导蛋白质正平衡,即蛋白质合成速率超过蛋白质降解速率。在这项研究中,我们研究了富含 EAA 的饮食在调节肌肉蛋白质稳态中的作用及其对 DEX 诱导的肌肉萎缩模型中葡萄糖代谢的影响。给小鼠喂食正常食物或富含 EAA 的食物,并在 10 天内每天注射 DEX。我们使用跑步机跑步和爬梯练习测定肌肉质量和功能,使用 D2O 标记方法测定蛋白质动力学,使用免疫印迹分析测定分子信号传导,并在口服葡萄糖耐量试验 (OGTT) 期间使用 U-13C6 葡萄糖示踪剂测定葡萄糖代谢。富含 EAA 的饮食增加了肌肉质量、力量和肌原纤维蛋白合成率,同时 OGTT 期间葡萄糖代谢得到改善(即血浆胰岛素浓度降低和胰岛素敏感性增加)。 U-13C6 葡萄糖追踪显示,富含 EAA 的饮食增加了葡萄糖摄取和随后的糖酵解通量。总之,我们的结果表明,富含 EAA 的饮食通过刺激肌原纤维蛋白合成来减轻 DEX 诱导的肌肉萎缩,这与改善葡萄糖代谢有关。
Dexamethasone (DEX) induces dysregulation of protein turnover, leading to muscle atrophy and impairment of glucose metabolism. Positive protein balance, i.e., rate of protein synthesis exceeding rate of protein degradation, can be induced by dietary essential amino acids (EAAs). In this study, we investigated the roles of an EAA-enriched diet in the regulation of muscle proteostasis and its impact on glucose metabolism in the DEX-induced muscle atrophy model. Mice were fed normal chow or EAA-enriched chow and were given daily injections of DEX over 10 days. We determined muscle mass and functions using treadmill running and ladder climbing exercises, protein kinetics using the D2O labeling method, molecular signaling using immunoblot analysis, and glucose metabolism using a U-13C6 glucose tracer during oral glucose tolerance test (OGTT). The EAA-enriched diet increased muscle mass, strength, and myofibrillar protein synthesis rate, concurrent with improved glucose metabolism (i.e., reduced plasma insulin concentrations and increased insulin sensitivity) during the OGTT. The U-13C6 glucose tracing revealed that the EAA-enriched diet increased glucose uptake and subsequent glycolytic flux. In sum, our results demonstrate a vital role for the EAA-enriched diet in alleviating the DEX-induced muscle atrophy through stimulation of myofibrillar proteins synthesis, which was associated with improved glucose metabolism.
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