Metabolic and Molecular Physiology Research Group, MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Graduate Entry Medicine and Health, Derby DE22 3DT, UK.
J Physiol. 2013 Jun 1;591(11):2911-23. doi: 10.1113/jphysiol.2013.253203. Epub 2013 Apr 3.
Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses-fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is 'sensed' have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-(13)C2]Leu and [(2)H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A-V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70% vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling 90 min vs. 30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; -57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu.
骨骼肌质量的维持取决于蛋白质周转率的动态平衡（空腹损失-进食增益）。在所有营养素中，单一氨基酸亮氨酸（Leu）作为启动蛋白质合成的触发因素，具有最显著的合成代谢特征。虽然亮氨酸被“感知”的机制一直受到广泛关注，但作为支链氨基酸，亮氨酸可以在肌肉内分解代谢，因此亮氨酸的代谢物可能参与介导亮氨酸的合成代谢效应。我们的目的是测量亮氨酸及其代谢物 HMB 对肌肉蛋白质合成的反应。使用 [1,2-(13)C2]Leu 和 [(2)H5]苯丙氨酸示踪剂，以及 GC-MS/GC-C-IRMS，我们研究了 HMB 或 Leu 单独对 MPS（通过示踪剂掺入肌原纤维）的影响，并且对于 HMB，我们还测量了肌肉蛋白水解（通过动静脉（A-V）稀释）。口服 3.42 g 游离酸（FA-HMB）HMB（提供 2.42 g 纯 HMB）在血浆和肌肉中具有快速的生物利用度，并且与 3.42 g Leu 相似，刺激肌肉蛋白质合成（MPS；HMB +70%对 Leu +110%）。虽然 HMB 和 Leu 都增加了合成代谢信号（雷帕霉素靶蛋白；mTOR），但 Leu 更为明显（即 p70S6K1 信号在 90 分钟时比 HMB 时增加 30 分钟）。HMB 消耗还以胰岛素非依赖性方式减弱肌肉蛋白分解（MPB；-57%）。我们得出结论，外源性 HMB 诱导急性肌肉合成代谢（增加 MPS 和减少 MPB），尽管可能通过不同于 Leu 的独特机制。
