Wang Yuan, Li Xi, Li Na, Du Jiawei, Qin Xiaodong, Sun Xiqing, Wang Yongchun, Li Chengfei
Department of Aerospace Medical Training, School of Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, China.
Key Laboratory of Sports and Physical Fitness of the Ministry of Education, Beijing Sport University, Beijing 100084, China.
Biomolecules. 2024 Dec 26;15(1):14. doi: 10.3390/biom15010014.
Skeletal muscle atrophy, which is induced by factors such as disuse, spaceflight, certain medications, neurological disorders, and malnutrition, is a global health issue that lacks effective treatment. Hindlimb unloading is a commonly used model of muscle atrophy. However, the underlying mechanism of muscle atrophy induced by hindlimb unloading remains unclear, particularly from the perspective of the myocyte proteome and metabolism. We first used mass spectrometry for proteomic sequencing and untargeted metabolomics to analyze soleus muscle changes in rats with hindlimb unloading. The study found 1052 proteins and 377 metabolites (with the MS2 name) that were differentially expressed between the hindlimb unloading group and the control group. Proteins like ACTN3, MYH4, MYBPC2, and MYOZ1, typically found in fast-twitch muscles, were upregulated, along with metabolism-related proteins GLUL, GSTM4, and NDUFS4. Metabolites arachidylcarnitine and 7,8-dihydrobiopterin, as well as pathways like histidine, taurine, and hypotaurine metabolism, were linked to muscle atrophy. Protein and metabolism joint analyses revealed that some pathways, such as glutathione metabolism, ferroptosis, and lysosome pathways, were likely to be involved in soleus atrophy. In this study, we have applied integrated deep proteomic and metabolomic analyses. The upregulation of proteins that are expressed in fast-twitch fibers indicates the conversion of slow-twitch fibers to fast-twitch fibers under hindlimb unloading. In addition, some differentially abundant metabolites and pathways revealed the important role of metabolism in muscle atrophy of the soleus. As shown in the graphical abstract, our study provides insights into the pathogenesis and treatment of muscle atrophy that results from unloading by integrating proteomics and metabolomics of the soleus muscles.
骨骼肌萎缩是一个全球性的健康问题，缺乏有效的治疗方法，它由废用、太空飞行、某些药物、神经疾病和营养不良等因素引起。后肢卸载是一种常用的肌肉萎缩模型。然而，后肢卸载诱导肌肉萎缩的潜在机制仍不清楚，特别是从肌细胞蛋白质组和代谢的角度来看。我们首先使用质谱进行蛋白质组测序和非靶向代谢组学分析后肢卸载大鼠比目鱼肌的变化。研究发现后肢卸载组和对照组之间有1052种蛋白质和377种代谢物（具有MS2名称）差异表达。通常在快肌中发现的ACTN3、MYH4、MYBPC2和MYOZ1等蛋白质上调，以及与代谢相关的蛋白质GLUL、GSTM4和NDUFS4。代谢物花生酰肉碱和7,8-二氢生物蝶呤，以及组氨酸、牛磺酸和亚牛磺酸代谢等途径与肌肉萎缩有关。蛋白质和代谢联合分析表明，一些途径，如谷胱甘肽代谢、铁死亡和溶酶体途径，可能参与比目鱼肌萎缩。在本研究中，我们应用了综合深度蛋白质组学和代谢组学分析。快肌纤维中表达的蛋白质上调表明后肢卸载下慢肌纤维向快肌纤维的转化。此外，一些差异丰富的代谢物和途径揭示了代谢在比目鱼肌肌肉萎缩中的重要作用。如图形摘要所示，我们的研究通过整合比目鱼肌的蛋白质组学和代谢组学，为卸载引起的肌肉萎缩的发病机制和治疗提供了见解。
