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bioRxiv · 10.1101/2024.11.20.624215

Advancements in Inflammation Parallels Myopenia in Winnie Mice Model of Spontaneous Chronic Colitis

Sharma, S.·Debruin, D.·Nurgali, K.·Devereaux, J.·Hayes, A.·Duque, G.
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Abstract

BackgroundInflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation and systemic complications, including muscle wasting. Musculoskeletal conditions have remained an unappreciated aspect of IBD. This study aimed to describe the Winnie mouse models skeletal muscle phenotype and functional alterations. This model spontaneously develops chronic colitis that closely resembles human IBD. MethodsWinnie mice and C57BL/6 (littermate) controls were evaluated at 5-6 weeks (pre-colitis) and 15-16 weeks (active colitis). Assessments included disease activity, inflammation, muscle function tests, and ex vivo analyses of the soleus (SOL) and tibialis anterior (TA) muscles for mass and histology. ResultsAt 5-6 weeks, Winnie mice showed no disease activity or muscle changes. At 15 weeks, Winnie mice exhibited significantly higher disease activity index (DAI) and elevated lipocalin-2 (LCN-2) levels than controls. SOL and TA muscles showed decreased weights and fibre sizes, which correlated significantly with LCN-2 levels. Wheel-running activity was reduced, which correlated with increased LCN-2 levels and DAI. DAI negatively correlated with muscle mass and fibre size. Grip strength remained unaltered despite these changes. ConclusionThe Winnie mouse model develops significant skeletal muscle alterations paralleling intestinal inflammation progression, characterized by reduced muscle mass and size with preserved strength but impaired functional endurance capacity. These findings establish the Winnie model as a valuable tool for investigating IBD-associated muscle wasting. Key Messages1. What is already known? O_LIInflammatory bowel disease (IBD) is associated with systemic complications, including muscle dysfunction. C_LI 2. What is new here? O_LIThe Winnie mouse model of chronic colitis develops skeletal muscle alterations that correlate with the progression of intestinal inflammation. C_LIO_LIMuscle changes in Winnie mice include reduced muscle mass, decreased fibre size, and, functional decline but preserved grip strength. C_LI 3. How can this study help patient care? O_LIThis research highlights the importance of monitoring muscle health in IBD patients and suggests potential targets for interventions to preserve muscle function. C_LIO_LIThe Winnie model provides a valuable tool for testing therapies aimed at addressing muscle dysfunction in IBD. C_LI

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Sharma, S., Debruin, D., Nurgali, K., Devereaux, J., Hayes, A., Duque, G.. 2024-11-21. Advancements in Inflammation Parallels Myopenia in Winnie Mice Model of Spontaneous Chronic Colitis. https://doi.org/10.1101/2024.11.20.624215

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