He Xu, Li Yan, Chen Jun, Huang Yan, Zhou Ying, Li Yang, Quan Jing
Department of Geriatrics, The First People's Hospital of Yunnan Province, No. 157 Jinbi Road, Xishan District, Kunming, 650032, Yunnan, China.
The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, 650032, Yunnan, China.
Biogerontology. 2025 Jun 18;26(4):120. doi: 10.1007/s10522-025-10262-7.
Muscle atrophy, resulting from physical inactivity or protein deficiency, is a significant health concern. β-hydroxy-β-methylbutyrate (HMB) has potential in preserving muscle mass, but its mechanisms in various atrophy-inducing conditions are not fully understood. This study aimed to investigate HMB's effects on muscle atrophy induced by inactivity and protein deprivation, and to elucidate the underlying molecular mechanisms. Rats were subjected to inactivity or protein-deficient diets with or without HMB supplementation. Muscle morphology, strength, and biochemical parameters were assessed. In vitro studies using C2C12 myoblasts and mouse skeletal muscle satellite cells exposed to interleukin-6 (IL-6) explored molecular pathways involved in HMB's protective effects. Inactivity and protein deprivation led to muscle atrophy, reduced strength, and altered biochemical markers. HMB supplementation partially mitigated these effects, preserving muscle mass and function. HMB attenuated atrophy markers (Muscle Atrophy F-box and Muscle RING Finger 1 (MuRF1)) and maintained myogenic factor (Myogenin (MyoG)) levels. In vitro studies revealed that HMB's protective effects were mediated through the AKT/mTOR pathway, with concurrent regulation of autophagy pathways and preservation of mitochondrial function in both myoblasts and satellite cells. HMB specifically protected satellite cell viability and function through AKT-dependent mechanisms, maintaining protein synthesis and reducing apoptosis under IL-6-induced stress conditions. HMB supplementation shows protective effects against muscle atrophy induced by inactivity and protein deprivation, through multiple mechanisms including AKT/mTOR pathway activation, autophagy regulation, and maintenance of mitochondrial function in both myoblasts and satellite cells. These findings suggest HMB as a potential therapeutic strategy for preventing muscle atrophy in various clinical scenarios.
因缺乏身体活动或蛋白质缺乏导致的肌肉萎缩是一个重大的健康问题。β-羟基-β-甲基丁酸酯（HMB）在维持肌肉质量方面具有潜力，但其在各种导致萎缩的条件下的机制尚未完全了解。本研究旨在调查HMB对因缺乏活动和蛋白质剥夺引起的肌肉萎缩的影响，并阐明其潜在的分子机制。将大鼠置于有无HMB补充的缺乏活动或蛋白质缺乏的饮食条件下。评估肌肉形态、力量和生化参数。使用暴露于白细胞介素-6（IL-6）的C2C12成肌细胞和小鼠骨骼肌卫星细胞进行的体外研究探索了HMB保护作用所涉及的分子途径。缺乏活动和蛋白质剥夺导致肌肉萎缩、力量降低和生化标志物改变。补充HMB部分减轻了这些影响，维持了肌肉质量和功能。HMB减弱了萎缩标志物（肌肉萎缩F盒和肌肉环形指蛋白1（MuRF1））并维持了生肌因子（肌细胞生成素（MyoG））水平。体外研究表明，HMB的保护作用是通过AKT/mTOR途径介导的，同时调节自噬途径并维持成肌细胞和卫星细胞中的线粒体功能。HMB通过AKT依赖性机制特异性地保护卫星细胞的活力和功能，在IL-6诱导的应激条件下维持蛋白质合成并减少细胞凋亡。补充HMB通过多种机制，包括激活AKT/mTOR途径、调节自噬以及维持成肌细胞和卫星细胞中的线粒体功能，对因缺乏活动和蛋白质剥夺引起的肌肉萎缩具有保护作用。这些发现表明HMB作为一种潜在的治疗策略，可用于预防各种临床情况下的肌肉萎缩。
