Treadmill Exercise is Associated with Intestinal Barrier and Cardiac Nlrp3 Gene Expression Changes in Diabetic Mice

This study investigated associations between exercise, intestinal barrier-related gene expression, and cardiac Nlrp3 inflammasome-related gene expression in a diabetic mouse model. Metabolic dysregulation was induced in male C57BL/6J mice using a high-fat diet combined with low-dose streptozotocin, followed by 8 weeks of treadmill exercise (5° slope, 12 m/min, 20-50 min/day, 5 days/week). Compared with sedentary diabetic mice, exercised mice showed lower fasting glucose, insulin resistance, and serum lipid levels, along with higher colonic Occludin mRNA expression (relative expression: 0.38 ± 0.04 in diabetic mice vs. 0.79 ± 0.05 in exercised mice, P < 0.001), lower cardiac Nlrp3, IL-1β, TNF-α, Col1a1, and Tgfb1 mRNA expression, and a lower Bax/Bcl-2 mRNA ratio (3.06 ± 0.19 vs. 1.48 ± 0.10, P < 0.001). Fecal qPCR analysis of six selected taxa showed that exercise was associated with increased relative abundances of Akkermansia muciniphila (0.31 ± 0.04 to 0.84 ± 0.07) and Lactobacillus (0.48 ± 0.05 to 1.01 ± 0.07) and decreased Escherichia coli (3.84 ± 0.33 to 1.68 ± 0.13, P < 0.01). In exercised mice, A. muciniphila abundance was negatively correlated with cardiac Nlrp3 mRNA expression (R = -0.81, P = 0.0046). These correlational findings indicate associations among exercise, cardiac and intestinal transcriptional changes, and selected gut microbial taxa in diabetic mice but do not establish causal relationships. All molecular findings are limited to mRNA-level changes and do not demonstrate intestinal barrier function, inflammasome activation, myocardial fibrosis, apoptosis, or other functional or protein-level effects.