Progressive Myopenia and Functional Decline in the Winnie Mouse Model of Chronic Colitis

Area of Science:

• Gastroenterology
• Muscle Physiology
• Inflammatory Bowel Disease Research

Background:

• Muscle wasting is a significant contributor to inflammatory bowel disease (IBD) disability.
• The relationship between colitis severity and muscle impairment across disease stages is not well understood.

Purpose of the Study:

• To investigate skeletal muscle mass, fiber morphology, and physical performance in the Winnie mouse model of chronic colitis.
• To assess how colitis progression impacts muscle health in both male and female mice at different disease stages.

Main Methods:

• Utilized the Winnie mouse model (Muc2 mutant) and wild-type littermates, assessing cohorts at 5 weeks (pre-colitis) and 15 weeks (pronounced colitis).
• Measured disease activity index (DAI), fecal lipocalin-2 (LCN-2), voluntary wheel-running performance, and muscle mass (soleus, tibialis anterior).
• Analyzed muscle fiber morphology using minimal Feret's diameter distributions and performed correlation analyses between inflammation markers, muscle parameters, and physical activity.

Main Results:

• At 5 weeks, Winnie mice showed no significant muscle deficits or overt disease.
• By 15 weeks, mice exhibited marked colitis (increased DAI, LCN-2), reduced wheel-running performance, decreased muscle mass, and smaller muscle fiber diameters.
• Significant correlations were found between fecal LCN-2, muscle mass/size, and running performance, indicating a link between gut inflammation and muscle dysfunction.

Conclusions:

• Spontaneous colitis progression in Winnie mice leads to significant skeletal muscle impairment, including reduced mass, myopathy, and decreased physical activity.
• The Winnie mouse model serves as a valuable preclinical tool for studying the mechanisms of muscle wasting associated with IBD.
• These findings highlight the clinical relevance of investigating muscle wasting in the context of IBD progression.