BACKGROUND Sarcopenia is an aging-induced deterioration of skeletal muscle mass and function. Low-magnitude high-frequency vibration (LMHFV) was shown to improve muscle functions and β-hydroxy-β-methylbutyrate (HMB) to increase muscle mass and strength. Muscle-derived stem cells (MDSCs) are progenitor cells important for muscle regeneration. We hypothesized that LMHFV and HMB could retard sarcopenia by reducing fat infiltration through inhibiting adipogenesis in MDSCs. METHODS Senescence-accelerated mouse P8 male mice were randomized into control (CTL), HMB, LMHFV (VIB), and combined (COM) groups. Interventions started at age of month 7 and assessed at 1, 2, and 3 months post-intervention by densitometry, histology, and functional tests. In vitro, MDSCs isolated from gastrocnemius of senescence-accelerated mouse P8 mice were characterized, randomized into CTL, VIB, HMB, and COM groups, and assessed by oil red O staining, mRNA, and protein expression. RESULTS At 2 months post-intervention, percentage lean mass of HMB, VIB, and COM groups were significantly higher than CTL group. Twitch, tetanic, and specific tetanic forces of COM group were higher, while specific twitch force of both VIB and COM groups were higher. Grip strength of HMB, VIB, and COM groups were higher. Histologically, both VIB and COM groups presented lower oil red O area than CTL group. Type I muscle fibre in CTL group was higher than HMB, VIB, and COM groups. MDSC were detected in situ by immunofluorescence stain with stem cell antigen-1 signals confirmed with higher β-catenin expression in the COM group. The observations were also confirmed in vitro, MDSCs in the HMB, VIB, and COM groups presented lower adipogenesis vs. the CTL group. β-Catenin mRNA and protein expressions were lower in the CTL group while their relationship was further validated through β-catenin knock-down approach. CONCLUSIONS Our results showed that combined LMHFV and HMB interventions enhanced muscle strength and decreased percentage fat mass and intramuscular fat infiltration as compared with either treatment alone. Additive effect of LMHFV and HMB was demonstrated in β-catenin expression than either treatment in MDSCs and altered cell fate from adipogenesis to myogenesis, leading to inhibition of intramuscular lipid accumulation. Wnt/β-catenin signalling pathway was found to be the predominant regulatory mechanism through which LMHFV and HMB combined treatment suppressed MDSCs adipogenesis.

中文翻译：

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振动和β-羟基-β-甲基丁酸酯治疗可抑制肌肉减少症患者肌肉内的脂肪浸润和成脂分化。

背景技术少肌症是由衰老引起的骨骼肌质量和功能的退化。低强度高频振动（LMHFV）被证明可以改善肌肉功能，而β-羟基-β-甲基丁酸酯（HMB）可以增加肌肉质量和力量。肌肉来源的干细胞（MDSC）是对肌肉再生很重要的祖细胞。我们假设LMHFV和HMB可以通过抑制MDSCs的脂肪生成来减少脂肪浸润，从而延迟肌肉减少症。方法衰老加速小鼠P8雄性小鼠随机分为对照组（CTL），HMB，LMHFV（VIB）和组合（COM）组。干预始于第7个月，并在干预后的1、2和3个月通过光密度测定，组织学和功能测试进行评估。在体外，对从衰老加速的小鼠P8小鼠腓肠肌分离的MDSC进行了表征，随机分为CTL，VIB，HMB和COM组，并通过油红O染色，mRNA和蛋白质表达进行评估。结果干预后2个月，HMB，VIB和COM组的瘦肉率显着高于CTL组。COM组的抽搐，强直和比强直肌力较高，而VIB和COM组的抽搐，强直和比肌强力均较高。HMB，VIB和COM组的握力较高。组织学上，VIB组和COM组的油红O面积均低于CTL组。CTL组的I型肌纤维高于HMB，VIB和COM组。通过免疫荧光染色在原位检测MDSC，其中干细胞抗原-1信号在COM组中被证实具有较高的β-catenin表达。HMB，VIB，与CTL组相比，COM组的成脂率更低。CTL组中β-cateninmRNA和蛋白表达较低，而它们之间的关系通过β-catenin敲除法得到进一步证实。结论我们的研究结果表明，与单独的两种治疗方法相比，LMHFV和HMB联合干预措施可增强肌肉强度，并减少脂肪量和肌内脂肪浸润百分比。LMHFV和HMB的相加作用在MDSCs中的β-catenin表达中得到了证实，并且从脂肪形成到肌生成均改变了细胞命运，从而导致了肌肉内脂质蓄积的抑制。发现Wnt /β-catenin信号通路是LMHFV和HMB联合治疗抑制MDSCs脂肪形成的主要调控机制。CTL组中β-cateninmRNA和蛋白表达较低，而它们之间的关系通过β-catenin敲除法得到进一步证实。结论我们的研究结果表明，与单独的两种治疗方法相比，LMHFV和HMB联合干预措施可增强肌肉强度，并减少脂肪量和肌内脂肪浸润百分比。LMHFV和HMB的相加作用在MDSCs中的β-catenin表达中得到了证实，并且从脂肪形成到肌生成均改变了细胞命运，从而导致了肌肉内脂质蓄积的抑制。发现Wnt /β-catenin信号通路是LMHFV和HMB联合治疗抑制MDSCs脂肪形成的主要调控机制。CTL组中β-cateninmRNA和蛋白表达较低，而它们之间的关系通过β-catenin敲除法得到进一步证实。结论我们的研究结果表明，与单独的两种治疗方法相比，LMHFV和HMB联合干预措施可增强肌肉强度，并减少脂肪量和肌内脂肪浸润百分比。LMHFV和HMB的相加作用在MDSCs中的β-catenin表达中得到了证实，并且从脂肪形成到肌生成均改变了细胞命运，从而导致了肌肉内脂质蓄积的抑制。发现Wnt /β-catenin信号通路是LMHFV和HMB联合治疗抑制MDSCs脂肪形成的主要调控机制。