Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased elF4F formation
Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased elF4F formation
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DOI：
10.1093/jn/130.2.139
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发表时间：
2000-02-01
影响因子：
4.2
通讯作者：
Jefferson, LS
中科院分区：
文献类型：
--
作者：
Anthony, JC;Anthony, TG;Jefferson, LS
我们研究了骨骼肌对单独或与碳水化合物联合口服亮氨酸的蛋白质合成反应。雄性大鼠自由进食（F）或禁食18小时;然后向禁食大鼠给予盐水（S）、碳水化合物（CHO）、亮氨酸（L）或碳水化合物加亮氨酸（CL）的组合，CHO和CL餐的热量相等，并提供每日能量需求的15%，L和CL餐各提供270 mg亮氨酸。肌肉蛋白质合成量在给药后1h为F的65%（P < 0.01）。伴随着较低的蛋白质合成率，翻译抑制蛋白，真核起始因子（eIF）4 E-结合蛋白1（4 E-BP-1）的磷酸化，在S中较少，导致更大的关联4 E-BP 1。eIF 4 E，并减少活性eIF 4G的形成。eIF 4 E复合物与F相比（P < 0.01），口服亮氨酸（L或Ct）而不是CHO恢复了与F相同的蛋白质合成，导致4 E-BP 1磷酸化是S的3倍（P < 0.01）。因此，形成4 E-BP 1. eIF 4 E被抑制，eIF 4G. eIF 4 E磷酸化水平在S组和CHO组显著高于其他各组（P < 0.01）。相比之下，在处理组之间未观察到eIF 2 α的磷酸化状态或eIF 2B的活性存在差异。血清胰岛素在CHO和CL中分别升高2.6和3.7倍，但L与S相比无显著差异（P < 0.05）。这些结果表明，亮氨酸刺激蛋白质合成骨骼肌增强eIF 4F的形成独立于血清胰岛素的增加。
We investigated the protein synthetic response of skeletal muscle to an orally administered dose of leucine given alone or in combination with carbohydrate. Male rats were freely fed (F) or food deprived for 18 h; food-deprived rats were then administered saline (S), carbohydrate (CHO), leucine (L) or a combination of carbohydrate plus leucine (CL), CHO and CL meals were isocaloric and provided 15% of daily energy requirements, L and CL meals each delivered 270 mg leucine. Muscle protein synthesis in S was 65% of F (P < 0.01) 1 h after meal administration. Concomitant with lower rates of protein synthesis, phosphorylation of the translational repressor, eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP-1), was less in S, leading to greater association of 4E-BP1 . eIF4E, and reduced formation of the active eIF4G . eIF4E complex compared with F (P < 0.01), Oral administration of leucine (L or Ct), but not CHO, restored protein synthesis equal to that in F and resulted in 4E-BP1 phosphorylation that was threefold greater than that of S (P < 0.01). Consequently, formation of 4E-BP1 . eIF4E was inhibited and eIF4G . elF4E was not different from F, The amount of eIF4E in the phosphorylated form was greater in S and CHO (P < 0.01) than in all other groups. In contrast, no differences in the phosphorylation state of eIF2 alpha or the activity of eIF2B were noted among treatment groups. Serum insulin was elevated 2.6- and 3.7-fold in CHO and CL, respectively, but was not different in L, compared with S (P < 0.05). These results suggest that leucine stimulates protein synthesis in skeletal muscle by enhancing eIF4F formation independently of increases in serum insulin.