Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation
Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation
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DOI：
10.1152/ajpendo.00510.2004
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发表时间：
2005-05-01
影响因子：
5.1
通讯作者：
Davis, TA
中科院分区：
文献类型：
--
作者：
Escobar, J;Frank, JW;Davis, TA
蛋白质合成的成年大鼠骨骼肌增加响应口服灌胃超生理剂量的亮氨酸。然而，尚未在新生儿中研究血浆亮氨酸生理性升高对蛋白质合成的影响，新生儿是对氨基酸和胰岛素高度敏感的合成代谢人群。因此，在本研究中，禁食猪动脉内输注亮氨酸（0、200或400 μ gmol.kg（-1）。h（-1）），并在60或120分钟后测量蛋白质合成。60分钟时，肌肉中的蛋白质合成增加，但肝脏中没有。然而，在120分钟时，肌肉中的蛋白质合成恢复到基线水平，但肝脏中的蛋白质合成降低到基线值以下。肌肉中蛋白质合成的增加与血浆亮氨酸增加1.5至3倍相关，而血浆胰岛素无变化。亮氨酸输注120分钟降低血浆必需氨基酸水平。在亮氨酸输注60和120分钟后，真核起始因子（eIF）-4E-结合蛋白-1（4 E-BP 1）、核糖体蛋白（rp）S6激酶和rpS 6的磷酸化增加，与其阻遏物4 E-BP 1相关的eIF 4 E的量减少。在肝脏中未观察到这些mRNA翻译生物标志物的变化。因此，血浆亮氨酸的生理增加刺激新生猪骨骼肌中的蛋白质合成，这与eIF 4F组装的eIF 4 E可用性增加有关。该反应似乎是胰岛素非依赖性的、底物依赖性的和组织特异性的。结果表明，支链氨基酸亮氨酸可以作为一种营养信号，刺激蛋白质合成的骨骼肌新生儿。
Protein synthesis in skeletal muscle of adult rats increases in response to oral gavage of supraphysiological doses of leucine. However, the effect on protein synthesis of a physiological rise in plasma leucine has not been investigated in neonates, an anabolic population highly sensitive to amino acids and insulin. Therefore, in the current study, fasted pigs were infused intra-arterially with leucine ( 0, 200, or 400 mu mol.kg(-1) . h(-1)), and protein synthesis was measured after 60 or 120 min. Protein synthesis was increased in muscle, but not in liver, at 60 min. At 120 min, however, protein synthesis returned to baseline levels in muscle but was reduced below baseline values in liver. The increase in protein synthesis in muscle was associated with increased plasma leucine of 1.5- to 3-fold and no change in plasma insulin. Leucine infusion for 120 min reduced plasma essential amino acid levels. Phosphorylation of eukaryotic initiation factor (eIF)-4E-binding protein-1 (4E-BP1), ribosomal protein (rp) S6 kinase, and rpS6 was increased, and the amount of eIF4E associated with its repressor 4E-BP1 was reduced after 60 and 120 min of leucine infusion. No change in these biomarkers of mRNA translation was observed in liver. Thus a physiological increase in plasma leucine stimulates protein synthesis in skeletal muscle of neonatal pigs in association with increased eIF4E availability for eIF4F assembly. This response appears to be insulin independent, substrate dependent, and tissue specific. The results suggest that the branched-chain amino acid leucine can act as a nutrient signal to stimulate protein synthesis in skeletal muscle of neonates.