Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Am J Physiol Endocrinol Metab. 2013 Aug 1;305(3):E416-28. doi: 10.1152/ajpendo.00618.2012. Epub 2013 Jun 11.
Muscle disuse atrophy is observed routinely in patients recovering from traumatic injury and can be either generalized resulting from extended bed rest or localized resulting from single-limb immobilization. The present study addressed the hypothesis that a diet containing 5% α-hydroxyisocaproic acid (α-HICA), a leucine (Leu) metabolite, will slow the loss and/or improve recovery of muscle mass in response to disuse. Adult 14-wk-old male Wistar rats were provided a control diet or an isonitrogenous isocaloric diet containing either 5% α-HICA or Leu. Disuse atrophy was produced by unilateral hindlimb immobilization ("casting") for 7 days and the contralateral muscle used as control. Rats were also casted for 7 days and permitted to recover for 7 or 14 days. Casting decreased gastrocnemius mass, which was associated with both a reduction in protein synthesis and S6K1 phosphorylation as well as enhanced proteasome activity and increased atrogin-1 and MuRF1 mRNA. Although neither α-HICA nor Leu prevented the casting-induced muscle atrophy, the decreased muscle protein synthesis was not observed in α-HICA-treated rats. Neither α-HICA nor Leu altered the increased proteasome activity and atrogene expression observed with immobilization. After 14 days of recovery, muscle mass had returned to control values only in the rats fed α-HICA, and this was associated with a sustained increase in protein synthesis and phosphorylation of S6K1 and 4E-BP1 of previously immobilized muscle. Proteasome activity and atrogene mRNA content were at control levels after 14 days and not affected by either treatment. These data suggest that whereas α-HICA does not slow the loss of muscle produced by disuse, it does speed recovery at least in part by maintaining an increased rate of protein synthesis.
肌肉废用性萎缩在创伤后康复的患者中经常观察到，可分为因长期卧床休息引起的全身性萎缩或因单肢固定引起的局限性萎缩。本研究旨在验证以下假设：饮食中添加 5%α-羟基异己酸（α-HICA），亮氨酸（Leu）的代谢产物，可减缓失用引起的肌肉质量损失和/或改善肌肉质量的恢复。成年 14 周龄雄性 Wistar 大鼠给予对照饮食或等氮等热量饮食，其中包含 5%α-HICA 或 Leu。通过单侧后肢固定（“石膏固定”）7 天来制造废用性萎缩，对侧肌肉用作对照。大鼠还进行了 7 天的石膏固定，并允许恢复 7 或 14 天。石膏固定降低了比目鱼肌的质量，这与蛋白质合成和 S6K1 磷酸化减少以及蛋白酶体活性增强以及atrogin-1 和 MuRF1 mRNA 增加有关。尽管 α-HICA 或 Leu 均不能预防石膏固定引起的肌肉萎缩，但在 α-HICA 处理的大鼠中未观察到肌肉蛋白合成减少。α-HICA 或 Leu 均未改变固定后观察到的蛋白酶体活性增加和萎缩基因表达。恢复 14 天后，仅在给予 α-HICA 的大鼠中，肌肉质量才恢复到对照值，这与先前固定的肌肉中蛋白质合成和 S6K1 以及 4E-BP1 的磷酸化持续增加有关。恢复 14 天后，蛋白酶体活性和萎缩基因 mRNA 含量恢复至对照水平，并且不受任何处理的影响。这些数据表明，尽管 α-HICA 不能减缓失用引起的肌肉损失，但至少在一定程度上通过维持较高的蛋白质合成率来加速恢复。
