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

Abstract

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 barrier-related 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.

Keywords:

• obesity
• high-fat diet
• moderate treadmill exercise
• gut microbiota
• gut barrier
• AMPK/CDX2 signal

Acknowledgments

This work is supported by the National Natural Science Foundation of China (grant number 32170496).

Disclosure

Dr Haiji Sun report's grants from the National Natural Science Foundation of China, during the conduct of the study. The authors report no other potential conflicts of interest for this work.