The Role of ADIPOQ and AMPK Signaling Pathway in Sarcopenia

To identify the hub genes involved in sarcopenia and analyze their correlation with lipid metabolism. Differentially expressed genes (DEGs) from sarcopenia/non-sarcopenia cohorts in GSE111006 and GSE111010 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. 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 (ADIPOQ) 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 (ADIPOQ) and AMPK were overexpressed in sarcopenia samples (p < 0.01). However, ADIPOQ and AMPK were no difference in the expression levels between individuals with T2DM and healthy individuals (p>0.05). This study identified a significant correlation between ADIPOQ, AMPK, and blood lipids in sarcopenia (ADIPOQ vs AMPK, p < 0.0001, r = 0.736; ADIPOQ vs HDL-C, p = 0.0003, r = -0.448; AMPK vs HDL-C, p = 0.001, r = -0.415). 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 ADIPOQ may regulate AMPK activity, affect lipid metabolism, and accelerate the occurrence and development of sarcopenia.