Integrated Proteomic and Metabolomic Analysis of Muscle Atrophy Induced by Hindlimb Unloading

ABSTRACT: Skeletal muscle atrophy, which is induced by factors such as disuse, spaceflight, certain medications, neurological disorders, and malnutrition, is a global health issue lacking effective treatment. Hindlimb unloading is a commonly used model for muscle atrophy. However, the underlying mechanism of muscle atrophy induced by hindlimb unloading remains unclear, particular from the perspective of 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 MS2 name) differentially expressed between HU group and CON 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, and pathways like histidine, taurine, and hypotaurine metabolism were linked to muscle atrophy. Protein and metabolism joint analysis 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 analysis. The upregulation of proteins which are expressed in fast-twitch fibers indicated the conversion of slow-twitch fibers to fast-twitch fibers under HU. Some metabolism-related proteins have been screened out. Besides, some differentially abundant metabolites and pathways revealed the important role of metabolism in the muscle atrophy of soleus. Our study provides insights into the pathogenesis and treatment of muscle atrophy that results from unloading by integrating the proteomics and metabolomics of soleus muscles.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Muscle

SUBMITTER: Jingyao Yan  

LAB HEAD: Li Chengfei

PROVIDER: PXD057671 | Pride | 2025-05-07

REPOSITORIES: Pride