Proteomics analysis reveals insights into the role of lipid metabolism in T2DM-related sarcopenia
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ABSTRACT: Sarcopenia has been recognized as an emerging complication of type 2 diabetes mellitus (T2DM). Currently, the pathogenesis of T2DM-related sarcopenia remains unclear. The aim of this study was to investigate the molecular mechanisms and potential therapeutic targets for T2DM-related sarcopenia. In this study, a T2DM-related sarcopenia mouse model was established using db/db mice. Proteins extracted from the gastrocnemius muscles of db/db mice and littermate control db/m mice were analyzed by a 4D label-free quantitative proteomics approach. A total of 131 upregulated and 68 downregulated proteins were identified as differentially expressed proteins (DEPs). Bioinformatics analysis revealed that DEPs were significantly enriched in lipid metabolism. Protein–protein interaction network analysis revealed that six hub proteins, including ACOX1, CPT2, ECI2, ACADVL, ACADL, and ECH1, were involved in the fatty acid oxidation. The hub protein-transcription factor-miRNA network was also constructed through the NetworkAnalyst tool. Finally, the hub proteins were validated by western blotting and immunohistochemistry and further confirmed to be significantly negatively correlated with the muscle mass and grip strength. Our study suggested that lipid metabolism, especially excessive fatty acid oxidation, may be a crucial contributor to the progression of T2DM-related sarcopenia and a common cause of the interrelationship between T2DM and sarcopenia.
INSTRUMENT(S): timsTOF Pro
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Skeletal Muscle
SUBMITTER: Wu Jingying
LAB HEAD: Jingying Wu
PROVIDER: PXD051462 | Pride | 2024-10-17
REPOSITORIES: Pride
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