Dissecting Semaglutide-dependent transcriptome response in obesity and osteoarthritis across tissues at single-cell resolution

The clinical observations of semaglutide cannot be fully explained by the classical GLP-1R signaling, indicating that semaglutide may exert its effects through a more complex multi tissue regulatory network. Based on this background, this study utilized high-fat diet (HFD) - induced obesity and surgery induced osteoarthritis (OA) models to simulate metabolic joint complications. By systematically collecting peripheral blood (PB), bone marrow (BM), liver, brain tissue, and skeletal muscle from C57BL/6 mice, and integrating 10x Genomics single-cell transcriptome sequencing, we constructed a cross tissue cell atlas that covers the immune, nervous, and motor metabolic systems under treatment with semaglutide. In addition, we compared the gene expression disturbances in mouse tissues after administration of semaglutide. Through these comparisons, we can more accurately decipher the specific effects of semaglutide treatment on gene expression in mice, thereby gaining a deeper understanding of their mechanisms of action in vivo.