Related Experiment Video

Updated: May 23, 2026

A Preclinical Model of Sepsis-Induced Myopathy with Disuse in Mice
04:01

A Preclinical Model of Sepsis-Induced Myopathy with Disuse in Mice

Published on: June 14, 2024

Targeting FoxO1/3a, NF-κB, and mTOR signaling attenuates muscle atrophy in sepsis

Donglin Fu1,2, Min Zhou1, Yingxiao Zhang1

  • 1Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Scientific Reports
|May 21, 2026
PubMed

Insights

Sepsis causes muscle wasting by activating protein breakdown pathways like autophagy and the ubiquitin-proteasome system (UPS). Targeting these pathways, including FoxO1/3a and NF-κB signaling, can prevent muscle loss and preserve function.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • Sepsis often results in skeletal muscle atrophy, a significant cause of morbidity and mortality.
  • The precise molecular mechanisms driving sepsis-induced muscle wasting are not fully understood.

Purpose of the Study:

  • To elucidate the molecular pathways responsible for sepsis-induced skeletal muscle atrophy.
  • To identify potential therapeutic targets for mitigating muscle loss during sepsis.

Main Methods:

  • Utilized a mouse model of cecal ligation and puncture (CLP) to simulate sepsis.
  • Employed lipopolysaccharide (LPS)-treated C2C12 myotubes to study cellular mechanisms.
  • Investigated the roles of autophagy, ubiquitin-proteasome system (UPS), calpain, FoxO1/3a, NF-κB, and mTOR signaling pathways.

Main Results:

  • Sepsis activated autophagy, UPS, and calpain pathways, leading to muscle wasting and functional decline.
  • Upregulated FoxO1/3a and NF-κB signaling, alongside suppressed mTOR activity, were observed.
  • Pharmacological inhibition or genetic deletion of key factors, notably MuRF1, attenuated muscle atrophy and preserved function.

Conclusions:

  • Sepsis-induced muscle loss is driven by the coordinated activation of proteolytic systems.
  • The FoxO1/3a, NF-κB, and mTOR signaling pathways are critical regulators of these proteolytic systems.
  • Targeting these pathways presents a promising therapeutic strategy for sepsis-related muscle atrophy.

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