Autophagy ablation in skeletal muscles worsens sepsis-induced muscle wasting, impairs whole-body metabolism, and decreases survival

• DOI: 10.1016/j.isci.2023.107475
• Publication Date: 2023-07-25T17:43:09Z
• Authors: Jean-Philippe Led...; Kayla Miguez; Marina Cefis; Julie Faitg; Alaa Moamer; Tomer Jordi Chaffer; Olivier Reynaud; Felipe E. Broering; Anwar Shams; Dominique Mayaki; Laurent Huck; Marco Sandri; Gilles Gouspillou; Sabah N.A. Hussain
• Keywords: Hypermetabolism

Septic patients frequently develop skeletal muscle wasting and weakness, resulting in severe clinical consequences adverse outcomes. Sepsis triggers sustained induction of autophagy, a key cellular degradative pathway, muscles. However, the impact enhanced autophagy on sepsis-induced dysfunction remains unclear. Using an inducible muscle-specific Atg7 knockout mouse model (Atg7iSkM-KO), we investigated functional importance sepsis using cecal ligation puncture model. Atg7iSkM-KO mice exhibited more phenotype response to sepsis, marked by wasting, hypoglycemia, higher ketone levels, decreased survival as compared with intact Atg7. deletion resulted accumulation mitochondrial dysfunction, although did not further worsen mice. Overall, our study demonstrates that inactivation muscles significant worsening metabolic dysfunctions negatively impacts survival.