Background: Recent studies implicate that 42% of inflammatory bowel disease (IBD) patients suffer from sarcopenia, the loss of muscle mass and strength, increasing the risk of falls and fall-related injuries. To determine the impact and molecular basis of IBD-associated sarcopenia, we sought to establish and characterize an experimental model for IBD-associated sarcopenia in vivo.
Methods: To induce colitis, male mice were treated with 0.75% dextran sodium sulfate (DSS) over a period of 14 days. Upon sacrifice, colon length and epithelial damage were determined to test local inflammation, and bone fragility was used as an indication for systemic inflammation. Muscle weight was measured, and morphology and fiber type distribution were assessed histologically. The molecular basis of sarcopenia was tested in M. quadriceps using qRT-PCR and by measuring the total protein content.
Results: The overall weight of Mm. quadriceps and gastrocnemius was reduced, and the muscle damage marker creatine kinase was slightly elevated upon DSS treatment. The successful induction of sarcopenia was further supported by the decrease in muscle fiber size, affecting both type 1 and 2 fibers. Moreover, these muscles displayed increased mRNA expression of the E3 ligases MuRF1 and Atrogin1/MAFbx, and accordingly, the overall protein content was reduced.
Conclusions: Our findings demonstrate that DSS-induced colitis leads to severe muscle loss in mice and therefore is a suitable model to induce inflammation-associated sarcopenia.
Keywords: DSS; colitis; inflammatory bowel diseases; mouse model; sarcopenia.
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