Disuse Exacerbates Sepsis-induced Muscle Weakness in Female Mice

Background: Sepsis is a severe and life-threatening condition characterized by a dysregulated host response to infection, leading to systemic inflammation and organ dysfunction affecting men and women equally. Survivors often endure prolonged periods of bed rest, which exacerbate muscle weakness and atrophy. Most research on sepsis-induced myopathy has focused on male animals under experimental conditions that do not mimic immobility. Here, we simulated the clinical conditions of sepsis and disuse to assess their influence on body mass, limb muscle mass, and force in female mice. Methods: Young adult (17-week-old) female C57Bl6 mice underwent either cecal ligation and puncture (CLP, n =18) or Sham (n =18) surgeries. Four days after surgery, animals were allocated to hindlimb suspension (CLP HLS, n=9; Sham HLS, n=9) or normal ambulation (CLP NA, n=9; Sham NA, n=9) for seven days. Terminal experiments were performed 7 days after HLS or NA conditions. We assessed body mass, muscle mass, ex vivo force (e.g., absolute and specific) production in soleus muscles. Results: We observed body mass loss when sepsis was combined with disuse (CLP HLS = -9 ± 2% vs. Sham NA -2 ± 4%, p = 0.003). In addition, we observed a 27.7% decrease in soleus mass in the CLP HLS group (5 ± 1 mg) compared to Sham NA (8 ± 1 mg), and a similar decrease of 26 % (6 ± 0.6 mg) in the Sham HLS group (p<0.05). Soleus absolute force was decreased by disuse, with a 35% reduction in the CLP HLS (152 ± 9 mN), a 32.3% reduction in the Sham HLS group (159 ± 11 mN), and a modest 10.6% reduction in the CLP NA group (210 ± 9 mN) compared to Sham NA (235 ± 13 mN; p<0.05). For specific force, only the CLP HLS group showed a decline in contractility (23.3%) relative to Sham NA (CLP HLS: 19 ± 1 vs. Sham NA: 25 ± 1 N/cm 2 ; p<0.05). Conclusion: Our findings demonstrate that disuse plays a major role in exacerbating muscle wasting and weakness in septic female mice. Furthermore, the combination of sepsis and disuse amplifies body mass loss and causes weakness that is independent of atrophy in female septic mice. This study was supported by National Institutes of Health (NIH) R21 AG072011 to OL This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.