Metabolomic profiling of skeletal muscle in GSDMD-knockout mice reveals distinct metabolic alterations in sepsis-induced myopathy.

Summary

Using GSDMD-knockout and wild-type mice in a sepsis model, non-targeted UHPLC-QE-MS metabolomics revealed substantial alterations in muscle metabolites and pathways (taurine/hypotaurine, amino acid, bile acid, oxidative stress, nucleotide metabolism). The study proposes metabolite panels as potential biomarkers and implicates GSDMD in regulating energy, amino-acid, lipid and redox metabolism in sepsis-associated myopathy.

Key Findings

• GSDMD knockout significantly altered skeletal muscle metabolome in septic mice, affecting taurine/hypotaurine, amino acid, bile acid, oxidative stress, and nucleotide metabolism.
• A panel of differential metabolites was identified that could serve as candidate biomarkers for sepsis-associated myopathy.
• Findings suggest GSDMD regulates energy, amino-acid, lipid and redox metabolic pathways in skeletal muscle during sepsis.

Clinical Implications

Identified metabolites could be developed as diagnostic markers for sepsis-associated myopathy and may point to metabolic pathways amenable to therapeutic modulation to preserve muscle function in sepsis survivors.

Limitations

• Study performed in mice; translational validity to human sepsis-associated myopathy requires confirmation.
• Sample size and time-course dynamics not detailed in abstract; longitudinal validation and mechanistic follow-up needed.

Future Directions

Validate identified metabolite panels in human sepsis cohorts, perform time-course studies, and test interventions targeting implicated metabolic pathways to preserve muscle function.