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

## TL;DR

This study shows that removing GSDMD in mice changes skeletal muscle metabolism during sepsis, potentially offering new ways to diagnose and treat sepsis-related muscle damage.

## Contribution

The study reveals novel metabolic pathways influenced by GSDMD deficiency in sepsis-induced skeletal muscle changes.

## Key findings

- GSDMD deficiency alters taurine, amino acid, and bile acid metabolism in skeletal muscle during sepsis.
- Metabolic changes suggest GSDMD regulates energy, lipid, and redox metabolism in sepsis.
- Potential biomarkers for muscle injury and repair were identified in GSDMD-knockout mice.

## Abstract

Gasdermin D (GSDMD), a key pyroptosis effector, is implicated in systemic inflammation during sepsis. However, its role in skeletal muscle metabolism remains largely unexplored.

GSDMD-knockout (GSDMD-KO) and wild-type (WT) mice were used to establish a septic model. Skeletal muscle samples were collected and subjected to non-targeted metabolomic analysis via UHPLC-QE-MS. Multivariate statistical analysis and KEGG pathway enrichment were performed to identify differential metabolites and explore the underlying metabolic alterations.

GSDMD knockout resulted in significant changes in skeletal muscle metabolism, notably in pathways related to taurine and hypotaurine metabolism, amino acid biosynthesis, bile acid biosynthesis, oxidative stress response, and nucleotide metabolism. These alterations suggest that GSDMD regulates energy, amino acid, lipid, and redox metabolism during sepsis. A panel of potential biomarkers was identified, which may contribute to muscle injury and repair.

GSDMD deficiency profoundly alters skeletal muscle metabolic profiles in sepsis. Identified metabolites may serve as diagnostic markers and therapeutic targets for sepsis-associated myopathy, offering insights into GSDMD’s role in muscle metabolism and potential intervention strategies.