Identification of hub genes and infiltrating immune cells in skeletal muscle in obesity.

BACKGROUND

Metabolic syndrome (MetS) refers to a cluster of metabolic disorders that are mainly caused by obesity. Skeletal muscle is a central component of systemic metabolism. However, the mechanism of skeletal muscle metabolic impairment in obesity remains unclear. This study aimed to identify key early biomarkers in skeletal muscle for the prevention and treatment of MetS in obesity.

METHODS

The GSE85439 dataset was downloaded from the Gene Expression Omnibus database. Gene set enrichment and immune cell infiltration analyses were performed for genome-wide genes. Differentially expressed genes (DEGs) between obese and control mice were screened and subjected to functional enrichment analysis, and a protein-protein interaction network was constructed. The results of the bioinformatics analysis were confirmed by immunofluorescence and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

RESULTS

Enrichment analysis indicated that the genes expressed in obese mice were mainly associated with acute inflammatory response. Immune cell infiltration analysis of 190 DEGs with consistent trends showed that the numbers of mast cells (MCs) and active dendritic cells were significantly higher in obese mice than in control mice. Immunofluorescence analysis confirmed that the number of MCs present in the skeletal muscle was higher in obese mice than in control mice, although no difference was observed in the active dendritic cell count. Functional enrichment analysis showed that the DEGs were mainly associated with transcriptional regulation. In the clusters of the protein-protein interaction network, four acute-phase-response genes (, , , and ) were significantly correlated with transcription-regulating genes (, , and ); these seven genes were identified as hub genes. The qRT-PCR results showed that the expression levels of , , , and were significantly higher in obese mice than in control mice; however, those of , , and did not differ significantly between the two groups.

CONCLUSIONS

The skeletal muscle of obese mice exhibits elevated MC infiltration and increased , , , and expression. The identification of these biomarkers has increased our understanding of the potential functional mechanisms of skeletal muscle in obesity. These potential biomarkers may serve as targets for the prevention and treatment of MetS.