Moderate Treadmill Exercise Modulates Gut Microbiota and Improves Intestinal Barrier in High-Fat-Diet-Induced Obese Mice via the AMPK/ CDX2 Signaling Pathway

Objective: The aim of this study was to investigate the effects of moderate treadmill exercise on gut microbiota, expression of proteins associated with gut barrier and to elucidate the mechanisms underlying their role in high-fat-diet-induced obese mice. Methods: Six-week-old male C57BL/6 mice were randomly divided into standard chow diet control group (SD + Sed, n=6), chow diet exercise group (SD + Exe, n=6), high-fat diet control group (HFD + Sed, n=6) and high-fat diet exercise group (HFD + Exe, n=6). Exercise groups were trained on a motorized treadmill for 45 min/d at running speeds of 12 m/min, 5 days/week, for 12 consecutive weeks. The body weight and fasting blood glucose of the mice were recorded before euthanasia. Thereafter, the mice were sacrificed and the alteration of adipose mass, colonic histopathology, gut microbiome and gut barrierrelated molecules were tested. Results: It was found that the moderate treadmill exercise prevented the development of adiposity and hyperglycemia and effectively improved the loss of diversity and the relative abundance of intestinal microflora induced by high-fat diet. Moreover, regular exercise reversed the intestinal pathology and elevated the number of goblet cells in obesity. Besides, compared with the sedentary obese mice, the protein expression levels of colonic ZO-1 and occludin were enhanced and AMPK/CDX2 signaling pathway was significantly upregulated in obese mice that underwent exercise. Conclusion: Long-term moderate treadmill exercise can markedly reduce the degree of obesity, modulate the colonic gut microbiota, and effectively activating AMPK/CDX2 signaling pathway to improve intestinal barrier in obese mice induced by high-fat diet.