Betaine Delayed Muscle Loss by Attenuating Samtor Complex Inhibition for mTORC1 Signaling Via Increasing SAM Level
Betaine Delayed Muscle Loss by Attenuating Samtor Complex Inhibition for mTORC1 Signaling Via Increasing SAM Level
复制标题
甜菜碱通过增加 SAM 水平减弱 Samtor 复合物对 mTORC1 信号传导的抑制来延迟肌肉损失
DOI：
10.1002/mnfr.202100157
复制
发表时间：
2021-06-25
影响因子：
5.2
通讯作者：
Zhu, Hui-Lian
中科院分区：
文献类型：
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作者：
Chen, Si;Lu, Xiao-Ting;Zhu, Hui-Lian
研究范围老年人肌肉萎缩是由于蛋白质合成受阻所致，对老年人健康构成威胁。本研究旨在探讨甜菜碱是否通过改善蛋白质合成来影响肌肉损失。方法和结果雄性C57 BL/6 J小鼠从12或15月龄开始饲养。小鼠分别用不含或含2%w/v甜菜碱的蒸馏水的AIN-93 M饮食喂养作为对照组或甜菜碱干预组（Bet）。对小鼠补充甜菜碱显示出更好的身体组成、握力和运动功能。Bet组大鼠骨骼肌形态学改变与成肌调节因子表达上调、肌球蛋白重链升高有关。甜菜碱通过将哺乳动物雷帕霉素靶蛋白复合物1蛋白激酶（mTORC 1）束缚在溶酶体膜上从而激活mTORC 1信号传导来促进肌肉蛋白合成。上述效应均具有时间依赖性（p < 0.05）。超高效液相色谱结果表明，甜菜碱通过甲硫氨酸循环增加S-腺苷-L-甲硫氨酸（SAM）。SAM传感器-Samtor-在C2 C12细胞中的过表达可以将mTORC 1从溶酶体中置换，从而抑制mTORC 1信号传导。添加甜菜碱通过增加SAM水平然后破坏Samtor复合物的相互作用来减弱这种抑制。结论甜菜碱可促进蛋白质合成，延缓增龄性肌肉萎缩。
Scope The muscle loss during aging results from the blunt of protein synthesis and poses threat to the elderly health. This study aims to investigate whether betaine affects muscle loss by improving protein synthesis. Methods and Results Male C57BL/6J mice are raised from age 12 or 15 months. Mice are fed with AIN-93M diet without or with 2% w/v betaine in distilled water as control group or betaine intervention group (Bet), respectively. Betaine supplementation to mice demonstrates better body composition, grip strength, and motor function. Muscle morphology upregulates expression of myogenic regulate factors, and elevates myosin heavy chain and also improves in Bet group. Betaine promotes muscle protein synthesis via tethering mammalian target of rapamycin complex1 protein kinase (mTORC1) on the lysosomal membrane thereby activating mTORC1 signaling. All these effects aforementioned are time-dependent (p < 0.05). Ultrahigh-performance liquid chromatography results show that betaine increases S-adenosyl-l-methionine (SAM) via methionine cycle. SAM sensor-Samtor-overexpression in C2C12 cells could displace mTORC1 from lysosome thereby inhibiting the mTORC1 signaling. Addition of betaine attenuates this inhibition by increasing SAM level and then disrupting interaction of Samtor complex. Conclusions These observations indicate that betaine could promisingly promote protein synthesis to delay age-related muscle loss.