Melatonin attenuates sepsis-induced muscle atrophy by regulating the PI3K/Akt signaling pathway.

Int Immunopharmacol

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China. Electronic address:

Published: January 2025

Background: In intensive care units, sepsis-related muscle atrophy is a severe complication of numerous diseases, yet the underlying mechanism and potential therapeutic options remain elusive. Recent research has identified melatonin as a promising candidate for attenuating organ dysfunction triggered by sepsis.

Methods: We used in vitro and in vivo models to simulate sepsis, C2C12 myotubes were treated with LPS, and the mice underwent cecal ligation and puncture (CLP) surgery. Following a pretreatment regimen involving melatonin and the AKT inhibitor MK-2206 2HCl, we analyzed changes in p-Akt and MuRF1 protein levels, fiber cross-sectional areas, and myotube diameters. The analyses included RNA sequencing, Western blotting, qRT-PCR, and immunofluorescence staining.

Results: Activation of the PI3K/Akt pathway in skeletal muscle occurred 24 h post-CLP surgery in mice. This was accompanied by upregulated MuRF1 expression and reduced muscle fiber cross-sectional area, which culminated in muscle atrophy. However, these detrimental effects were attenuated when the mice were pretreated with melatonin via intraperitoneal injection for seven consecutive days. Similarly, LPS treatment of C2C12 myotubes activated the PI3K/Akt pathway, elevated MuRF1 expression, and markedly reduced myotube diameter after 48 h, leading to muscle atrophy. Pretreatment of C2C12 myotubes with melatonin 24 h in advance mitigated these adverse effects. However, cotreatment of C2C12 myotubes with melatonin and MK-2206 2HCl attenuated the beneficial effects of melatonin.

Conclusion: Melatonin can attenuate sepsis-induced muscle atrophy by regulating the PI3K/Akt pathway.

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Source
http://dx.doi.org/10.1016/j.intimp.2024.113619DOI Listing

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