Semaglutide targets mitochondria to regulate metabolism and inflammation in sarcopenia and osteoarthritis

ABSTRACT: Metabolic and inflammatory diseases often coexist, and become important challenges facing global health. As a traditional anti-obesity drug, semaglutide is reported to have therapeutic effects in sarcopenia and osteoarthritis (OA), but its mechanism of action still needs to be explored. Here we employed single-cell sequencing analysis to analyze transcriptome changes cross various tissues of high-fat diet (HFD) and OA model mice, and found that semaglutide significantly improved the metabolic and inflammatory disorders of muscle tissue during HFD and OA. Mechanistically, we found that semaglutide could enhance muscle mitochondrial metabolism and mitophagy, alleviated the activation of inflammatory cytokines caused by hypoxia, and regulated the progression of sarcopenia and OA across tissues. Intramuscular injection of mitochondria, pre-stimulated by semaglutide, could significantly alleviate OA inflammation and pain symptoms. These findings reveal the mitochondrial regulatory mechanism in the muscle-OA axis and provide a new perspective for the application of semaglutide in OA treatment.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: yuchen tian  

LAB HEAD: Tian Yuchen

PROVIDER: PXD073074 | Pride | 2026-05-06

REPOSITORIES: Pride