E-44 Free Communication/Poster - Immunology III Friday, May 31, 2019, 7: 30 AM - 12: 30 PM Room: CC-Hall WA2
PURPOSE: To investigate the therapeutic effect of treadmill running against ulcerative colitis induced by high-fat diet (HFD) and mild dextran sulfate sodium (DSS) in wild-type (WT) mice.
METHODS: At age of 10 weeks, C57BL/6 male mice were assigned to either standard chow (SC, n=10) or HFD (n=10) or HFD+DSS (HFD+DSS, n=10) or HFD+exercise training+DSS (HFD+EX+DSS, n=10). Mice in the HFD+EX+DSS group was subjected to a moderate treadmill running with 50 minutes per session and 5 days per week for 11 weeks. Mice in the DSS groups were fed with DSS (2% w/v) in the drinking water during the last 3 weeks of the 11-week treatment period. Hepatic histology, hepatic genes of inflammation and fibrosis, and tight junction proteins in colon were assessed as primary outcomes.
RESULTS: HFD+DSS exacerbated hepatic steatosis in conjunction with greater weight loss, shortened colon length (p=0.02), enlarged spleen (p=0.03), and greater infiltration of neutrophils and monocytes into circulating blood (p<0.001 & p<0.001, respectively) and colon (p<0.001 & p<0.001, respectively) compared to HFD alone. The pathology of HFD+DSS-induced ulcerative colitis was accompanied by upregulated hepatic inflammatory and fibrosis genes such as Ly6d (p=0.020), Lgals (p=0.021), Timp-1 (p<0.001), Col1a1 (p<0.001) and increased serum inflammatory markers such as IL-6 (p<0.001), IL-17a (p<0.001), GRO-α (p=0.03), and MCP-1 (p=0.42), as well as downregulated colon tight junction proteins such as ZO-1 (p=0.01) and occludin (p=0.01). However, treadmill running alleviated the severity of colitis phenotypes induced by HFD+DSS treatment via suppression of upregulated hepatic inflammatory and fibrosis genes and stimulation of downregulated colon tight junction proteins.
CONCLUSION: The current findings suggest that exercise training alleviates the severity of HFD+DSS-induced ulcerative colitis by modulating genes of hepatic inflammation and fibrosis and colon tight junction proteins in WT mice.
Supported by the National Research Foundation funded by the Korean Government (NRF-2017R1A2B4007357).