Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.
Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.
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DOI：
10.1002/jcp.25960
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发表时间：
2017-10
影响因子：
5.6
通讯作者：
Lewis MP
中科院分区：
文献类型：
--
作者：
Martin NRW;Turner MC;Farrington R;Player DJ;Lewis MP
亮氨酸被认为对骨骼肌的生长很重要，因为它能够敏锐地激活mTORC1并促进肌肉蛋白质的合成，但关于它对骨骼肌大小和产生力量的能力的影响的数据很少。我们利用组织工程学的方法来测试在培养液中添加亮氨酸是否可以增强mTORC1信号、肌管生长和肌肉功能。MTORC1靶蛋白4EBP-1和RpS6的磷酸化与肌管肥大呈剂量依赖关系，5 mM和20 mM的亮氨酸诱导的作用相似，大于1 mM的作用。补充亮氨酸也能增加最大的收缩力；然而，尽管这似乎不会随着亮氨酸剂量的增加而增强，但这种作用可以通过与mTOR抑制剂雷帕霉素共同孵育而完全消除，这表明在亮氨酸存在的情况下增加的力量产生是mTOR敏感的。最后，通过使用电刺激来诱导工程化骨骼肌结构的慢性(24 小时)收缩，我们能够证明亮氨酸和肌肉收缩的作用是相加的，因为这两种刺激对最大收缩力的产生具有累积效应。这些结果扩展了我们目前对亮氨酸作为一种合成代谢营养辅助剂的有效性的认识，首次表明补充亮氨酸可以增强骨骼肌的功能能力，并进一步验证了利用工程骨骼肌进行肌肉生理营养调节的高度控制研究。
The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP‐1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co‐incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly‐controlled investigations into nutritional regulation of muscle physiology.
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DOI：
10.1083/jcb.200903131
发表时间：
2009-12-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Risson V;Mazelin L;Roceri M;Sanchez H;Moncollin V;Corneloup C;Richard-Bulteau H;Vignaud A;Baas D;Defour A;Freyssenet D;Tanti JF;Le-Marchand-Brustel Y;Ferrier B;Conjard-Duplany A;Romanino K;Bauché S;Hantaï D;Mueller M;Kozma SC;Thomas G;Rüegg MA;Ferry A;Pende M;Bigard X;Koulmann N;Schaeffer L;Gangloff YG
通讯作者：
Gangloff YG
影响因子：
7.1
作者：
Atherton, Philip J.;Etheridge, Timothy;Rennie, Michael J.
通讯作者：
Rennie, Michael J.
影响因子：
5.5
作者：
Churchward-Venne, Tyler A.;Burd, Nicholas A.;Phillips, Stuart M.
通讯作者：
Phillips, Stuart M.
影响因子：
4.8
作者：
Bian, Weining;Bursac, Nenad
通讯作者：
Bursac, Nenad
DOI：
10.1152/ajpendo.00353.2011
发表时间：
2012-03-01
影响因子：
5.1
作者：
Borgenvik, Marcus;Apro, William;Blomstrand, Eva
通讯作者：
Blomstrand, Eva