背景:随着衰老或在各种情况下,肌肉力量和耐力的丧失会对生活质量产生负面影响。阻力运动训练(RET)是提高肌肉质量和力量的最有力手段,但它通常不会导致耐力的提高。游离必需氨基酸(EAA)充当线粒体和肌原纤维蛋白合成的前体和刺激物,可能会赋予耐力和力量增益。因此,我们假设,除了通过RET增加力量外,每日摄入9种免费EAA的膳食补充剂可改善耐力.
方法:将雄性C57BL6J小鼠(9周龄)指定为对照(CON),EAA,RET(爬梯,每周3次),或联合治疗EAA和RET(EAA+RET)组。在干预前后评估了以力量或耐力为重点的身体功能。进行了几项分析,以更好地了解肌肉功能改善的机制。我们使用2H2O标记和质谱确定肌原纤维和线粒体蛋白质合成的累积速率;评估离体收缩特性和体外线粒体功能,评估神经肌肉接头(NMJ)稳定性,并评估了相关的分子单发途径。此外,全身和肌肉胰岛素敏感性以及葡萄糖代谢,使用高胰岛素-正常血糖钳夹进行评估。
结果:EAA+RET增加肌肉质量(10%,P<0.05)和强度(6%,P<0.05)比单独RET多,由于肌肉综合蛋白合成率提高(19%,P<0.05)伴随Akt1/mTORC1信号的激活。RET改善了肌肉质量(肌肉力量标准化为质量)(即,RET和EAA+RET)与久坐组(10%,P<0.05),与AchR簇大小增加和MuSK激活相关(P<0.05)。EAA+RET也比单独的RET提高了耐力(26%,P<0.05)通过增加线粒体蛋白质合成(53%,P<0.05)和DRP1激活(P<0.05)。通过激活mTORC1-DRP1信号轴,最大呼吸容量增加(P<0.05)。这些有利的作用伴随着基础葡萄糖代谢的改善(即,血糖浓度和内源性葡萄糖生产与CON,P<0.05)。
结论:用平衡的游离EAA和RET联合治疗可以通过增加肌肉蛋白质合成来有效提高耐力和肌肉力量,改善NMJ稳定性,并通过mTORC1-DRP1轴激活增强线粒体动力学,最终导致改善基础葡萄糖代谢。
BACKGROUND: Loss of muscle strength and endurance with aging or in various conditions negatively affects quality of life. Resistance exercise training (RET) is the most powerful means to improve muscle mass and strength, but it does not generally lead to improvements in endurance capacity. Free essential amino acids (EAAs) act as precursors and stimuli for synthesis of both mitochondrial and myofibrillar proteins that could potentially confer endurance and strength gains. Thus, we hypothesized that daily consumption of a dietary supplement of nine free EAAs with RET improves endurance in addition to the strength gains by RET.
METHODS: Male C57BL6J mice (9 weeks old) were assigned to control (CON), EAA, RET (ladder climbing, 3 times a week), or combined treatment of EAA and RET (EAA + RET) groups. Physical functions focusing on strength or endurance were assessed before and after the interventions. Several analyses were performed to gain better insight into the mechanisms by which muscle function was improved. We determined cumulative rates of myofibrillar and mitochondrial protein synthesis using 2H2O labelling and mass spectrometry; assessed ex vivo contractile properties and in vitro mitochondrial function, evaluated neuromuscular junction (NMJ) stability, and assessed implicated molecular singling pathways. Furthermore, whole-body and muscle insulin sensitivity along with glucose metabolism, were evaluated using a hyperinsulinaemic-euglycaemic clamp.
RESULTS: EAA + RET increased muscle mass (10%, P < 0.05) and strength (6%, P < 0.05) more than RET alone, due to an enhanced rate of integrated muscle protein synthesis (19%, P < 0.05) with concomitant activation of Akt1/mTORC1 signalling. Muscle quality (muscle strength normalized to mass) was improved by RET (i.e., RET and EAA + RET) compared with sedentary groups (10%, P < 0.05), which was associated with increased AchR cluster size and MuSK activation (P < 0.05). EAA + RET also increased endurance capacity more than RET alone (26%, P < 0.05) by increasing both mitochondrial protein synthesis (53%, P < 0.05) and DRP1 activation (P < 0.05). Maximal respiratory capacity increased (P < 0.05) through activation of the mTORC1-DRP1 signalling axis. These favourable effects were accompanied by an improvement in basal glucose metabolism (i.e., blood glucose concentrations and endogenous glucose production vs. CON, P < 0.05).
CONCLUSIONS: Combined treatment with balanced free EAAs and RET may effectively promote endurance capacity as well as muscle strength through increased muscle protein synthesis, improved NMJ stability, and enhanced mitochondrial dynamics via mTORC1-DRP1 axis activation, ultimately leading to improved basal glucose metabolism.