The Role of and AMPK Signaling Pathway in Sarcopenia.

Objective: To identify the hub genes involved in sarcopenia and analyze their correlation with lipid metabolism.

Methods: Differentially expressed genes (DEGs) from sarcopenia/non-sarcopenia cohorts in and datasets were cross-analyzed with diabetes-related genes (GeneCards). Key genes underwent functional enrichment and protein-protein interaction (PPI) network analysis. The expression and receiver operating characteristic (ROC) curve of the hub gene was analyzed in both datasets. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify hub gene levels in sarcopenia, type 2 diabetes (T2DM), and healthy samples.

Results: Twenty key genes were identified through differential expression and diabetes-related gene screening. Functional enrichment analysis revealed their involvement in external stimulus response, inflammatory regulation, extracellular processes, adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, and insulin signaling pathways (p<0.05). Adiponectin () emerged as the hub gene via PPI network analysis, showing significant overexpression in sarcopenia (GSE111006: p<0.01; GSE111010: p<0.05) with diagnostic AUCs of 0.944 (0.869-1.000) and 0.696 (0.471-0.920) respectively. Ultimately, 60 sarcopenia, 10 type 2 diabetes, 10 healthy samples were collected. Seventy percent of the samples exhibited abnormal lipid metabolism. Adiponectin and AMPK were overexpressed in sarcopenia samples ( < 0.01). However, and AMPK were no difference in the expression levels between individuals with T2DM and healthy individuals (>0.05). This study identified a significant correlation between , AMPK, and blood lipids in sarcopenia ( vs AMPK, < 0.0001, = 0.736; vs HDL-C, = 0.0003, = -0.448; AMPK vs HDL-C, = 0.001, = -0.415).

Conclusion: The present study confirms that glycolipid metabolism is a risk factor for sarcopenia. Both ADIPOQ and AMPK are overexpressed in sarcopenia and demonstrate a significant positive correlation. This study hypothesizes that may regulate AMPK activity, affect lipid metabolism, and accelerate the occurrence and development of sarcopenia.