Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion
Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion
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DOI：
10.1113/jphysiol.2008.160333
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发表时间：
2008-12-15
影响因子：
5.5
通讯作者：
Rennie, Michael J.
中科院分区：
文献类型：
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作者：
Glover, Elisa I.;Phillips, Stuart M.;Rennie, Michael J.
我们验证了这样一个假设，即增加血液中氨基酸（AA）的可用性可以抵消身体不活动导致的肌肉蛋白质合成减少。我们测定了年轻健康受试者（10名男性，2名女性，21 +/- 1岁；80.2 +/- 4.0 kg，平均+/- s.e.m）在吸收后状态和低剂量或高剂量(43和261 mg kg（-1) h(-1)）注射AA （10% Primene）后14天单侧膝关节固定对股四头肌肌纤维蛋白合成（MPS）的影响。肌肉横截面积（MRI）和峰值等距扭矩在固定腿中下降（分别为-5.0 +/- 1.2%和-25 +/- 3%，均P < 0.005），但在非固定腿中保持不变（均P < 0.6）。固定化诱导吸收后MPS率下降27%(固定化，0.027 +/- 0.003；非固定化，0.037 +/- 0.003% h(-1)；P < 0.001)。无论剂量如何，AA输注刺激了非固定腿部MPS的更大升高；4 h时，低剂量AA组MPS升高+54 +/- 12%，高剂量AA组升高+68 +/- 17% （P均< 0.001）。有证据表明，高剂量AA和p70S6k对Akt磷酸化的反应延迟，但mTOR、GSK3 β和eEF2对Akt磷酸化的反应无显著差异。黏附斑激酶（Tyr(576/577)）磷酸化水平在固定状态下降低（P < 0.05）。我们观察到固定后多泛素化蛋白含量没有变化。我们证实，14天的固定减少了吸收后状态的MPS，即使在高剂量的情况下，增加AA也会减少但不会消除这种减少。固定诱导的吸收后MPS下降以及对氨基酸的“合成代谢抵抗”可以解释固定诱导的肌肉萎缩的大部分原因。
We tested the hypothesis that increasing blood amino acid (AA) availability would counter the physical inactivity-induced reduction in muscle protein synthesis. We determined how 14 days of unilateral knee immobilization affected quadriceps myofibrillar protein synthesis (MPS) in young healthy subjects (10 men, 2 women, 21 +/- 1 years; 80.2 +/- 4.0 kg, mean +/- s.e.m.) in the post-absorptive state and after infusing AA (10% Primene) at low or high doses (43 and 261 mg kg(-1) h(-1)). Muscle cross-sectional area (MRI) and peak isometric torque declined in the immobilized leg (-5.0 +/- 1.2% and -25 +/- 3%, respectively, both P < 0.005), but were unchanged (all P > 0.6) in the non-immobilized leg. Immobilization induced a 27% decline in the rate of post-absorptive MPS (immobilized, 0.027 +/- 0.003: non-immobilized, 0.037 +/- 0.003% h(-1); P < 0.001). Regardless of dose, AA infusion stimulated a greater rise in MPS in the non-immobilized legs; at 4 h MPS was greater by +54 +/- 12% with low dose and +68 +/- 17% with high dose AA infusion (both P < 0.001). There was some evidence of delayed responsiveness of phosphorylation of Akt to high doses of AA and p70S6k at both doses but no marked differences in that of mTOR, GSK3 beta or eEF2. Phosphorylation of focal adhesion kinase (Tyr(576/577)) was reduced (P < 0.05) with immobilization. We observed no change in polyubiquitinated protein content after immobilization. We confirm that 14 days of immobilization reduces MPS in the post-absorptive state and this diminution is reduced but not abolished by increased provision of AA, even at high rates. The immobilization-induced decline in post-absorptive MPS with the 'anabolic resistance' to amino acids can account for much of immobilization-induced muscle atrophy.