Integrated Proteomic and Metabolomic Analysis of Muscle Atrophy Induced by Hindlimb Unloading
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 o...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/1/14 |
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| Summary: | 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. |
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| ISSN: | 2218-273X |