Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 0608638, Japan.
Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 0608638, Japan.
Life Sci. 2020 Jun 1;250:117593. doi: 10.1016/j.lfs.2020.117593. Epub 2020 Mar 28.
Sarcopenia is characterized by muscle mass and strength loss and reduced physical activity. Branched-chain amino acids (BCAAs) were recently described as an activator of protein synthesis via mammalian target of rapamycin (mTOR) signaling for muscle atrophy. In cardiovascular diseases, excessive activation of the renin-angiotensin system may induce an imbalance of protein synthesis and degradation, and this plays a crucial role in muscle atrophy. We investigated the effects of BCAAs on angiotensin II (Ang II)-induced muscle atrophy in mice.
We administered Ang II (1000 ng/kg/min) or vehicle to 10-12-week-old male C57BL/6J mice via subcutaneous osmotic minipumps for 4 weeks with or without BCAA supplementation (3% BCAA in tap water).
The skeletal muscle weight/tibial length and cross-sectional area were smaller in the Ang II mice than the vehicle mice; these changes were induced by an imbalance of protein synthesis and degradation signaling such as Akt/mTOR and MuRF-1/Atrogin-1. Compared to the Ang II mice, the mTOR signaling was significantly activated and Ang II-induced muscle atrophy was ameliorated in the Ang II + BCAA mice, and this attenuated the reduction of exercise capacity. Notably, the decrease of muscle weight/tibial length in the fast-twitch dominant muscles (e.g., the extensor digitorum longus) was significantly ameliorated compared to that in the slow-twitch dominant muscles (e.g., soleus). Histologically, the effect of BCAA was larger in fast-twitch than slow-twitch fibers, which may be related to the difference in BCAA catabolism.
BCAA supplementation could contribute to the prevention of skeletal muscle atrophy induced by Ang II.
肌肉减少症的特征是肌肉质量和力量下降以及身体活动减少。支链氨基酸（BCAAs）最近被描述为通过哺乳动物雷帕霉素靶蛋白（mTOR）信号通路激活肌肉萎缩的蛋白质合成。在心血管疾病中，肾素-血管紧张素系统的过度激活可能导致蛋白质合成和降解的失衡，这在肌肉萎缩中起着关键作用。我们研究了 BCAAs 对血管紧张素 II（Ang II）诱导的小鼠肌肉萎缩的影响。
我们通过皮下渗透微型泵向 10-12 周龄雄性 C57BL/6J 小鼠输注 Ang II（1000ng/kg/min）或载体，持续 4 周，并在有或没有 BCAAs 补充（自来水中 3%BCAA）的情况下进行补充。
Ang II 组小鼠的骨骼肌重量/胫骨长度和横截面积小于载体组小鼠；这些变化是由蛋白质合成和降解信号的失衡引起的，如 Akt/mTOR 和 MuRF-1/Atrogin-1。与 Ang II 组相比，Ang II+BCAA 组的 mTOR 信号明显激活，Ang II 诱导的肌肉萎缩得到改善，运动能力下降得到缓解。值得注意的是，与慢肌纤维（如比目鱼肌）相比，快肌纤维（如伸趾长肌）的肌肉重量/胫骨长度下降得到了显著改善。组织学上，BCAA 的作用在快肌纤维中大于慢肌纤维，这可能与 BCAA 分解代谢的差异有关。
BCAA 补充可能有助于预防 Ang II 诱导的骨骼肌萎缩。
