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

Leduc-Gaudet, J.-P., Miguez, K., Cefis, M., Faitg, J., Moamer, A., Chaffer, T. J., Reynaud, O., Broering, F. E., Shams, A., Mayaki, D., Huck, L., Sandri, M., Gouspillou, G. et Hussain, S. N. A. (2023). Autophagy ablation in skeletal muscles worsens sepsis-induced muscle wasting, impairs whole-body metabolism, and decreases survival. iScience, 26 (8). Article 107475. ISSN 2589-0042 DOI 10.1016/j.isci.2023.107475

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Summary

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

Type de document:	Article
Mots-clés libres:	Genetics Human metabolism Musculoskeletal medicine
Date de dépôt:	17 juin 2024 13:10
Dernière modification:	17 juin 2024 13:10
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/11358

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