Causal Implication of CD52-Driven Immune Dysregulation in Sarcopenic Obesity: Integrating Mendelian Randomization and Multiomics Profiling.

PURPOSE: Sarcopenic obesity patients are likely to develop exacerbated metabolic dysfunction, while the mechanism linking sarcopenia and obesity is still unclear. This study aims to explore hub genes and immune-metabolic dysregulation related to the molecular pathogenesis of sarcopenia and obesity.

METHODS

We used a public Gene Expression Omnibus (GEO) dataset to identify hub genes associated with sarcopenia and obesity. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI), differentially expressed gene (DEG) analysis, GO/KEGG functional enrichment analyses and immune cell infiltration analysis were conducted to identify hub genes. Subsequently, these hub genes underwent multi-level validation.

RESULTS

Integrated bioinformatics analysis identified 16 shared hub genes linked to the sarcopenia-obesity nexus. These genes were mainly enriched in immune-related pathways, as supported by immune infiltration profiling. External validation in independent cohorts confirmed CD52 as a common and central gene in both sarcopenia and obesity datasets, showing significant associations with immune cell characteristics. Mendelian randomization analysis indicated potential causal links between genetically predicted CD52 levels and reduced hand grip strength as well as increased body mass index, and these results were further supported by PCR assays in clinical samples.

CONCLUSION

The integrative analysis indicates that CD52 may function as a novel immunometabolic mediator in SO pathogenesis, underscoring its potential as a candidate biomarker for further study.