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适度跑步机运动通过AMPK/CDX2信号通路调节高脂饮食诱导的肥胖小鼠肠道微生物群并改善肠道屏障

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

作者信息

Wang Jing, Zhang Qiang, Xia Jie, Sun Haiji

机构信息

Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai, 200241, People's Republic of China.

School of Physical Education & Health, East China Normal University, Shanghai, 200241, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2022 Jan 20;15:209-223. doi: 10.2147/DMSO.S346007. eCollection 2022.

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.

摘要

目的

本研究旨在探讨适度跑步机运动对肠道微生物群、肠道屏障相关蛋白表达的影响,并阐明其在高脂饮食诱导的肥胖小鼠中发挥作用的机制。

方法

将6周龄雄性C57BL/6小鼠随机分为标准饲料对照组(SD + Sed,n = 6)、饲料运动组(SD + Exe,n = 6)、高脂饮食对照组(HFD + Sed,n = 6)和高脂饮食运动组(HFD + Exe,n = 6)。运动组在电动跑步机上以12米/分钟的速度训练45分钟/天,每周5天,连续训练12周。在安乐死之前记录小鼠的体重和空腹血糖。此后,处死小鼠并检测脂肪量、结肠组织病理学、肠道微生物群和肠道屏障相关分子的变化。

结果

发现适度跑步机运动可预防肥胖和高血糖的发展,并有效改善高脂饮食诱导的肠道微生物群多样性丧失和相对丰度。此外,规律运动可逆转肠道病理学变化并增加肥胖小鼠中杯状细胞的数量。此外,与久坐的肥胖小鼠相比,运动的肥胖小鼠结肠中ZO-1和闭合蛋白的蛋白表达水平增强,AMPK/CDX2信号通路显著上调。

结论

长期适度跑步机运动可显著降低肥胖程度,调节结肠肠道微生物群,并有效激活AMPK/CDX2信号通路以改善高脂饮食诱导的肥胖小鼠的肠道屏障。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ba0/8789310/3ce3f592b9ec/DMSO-15-209-g0001.jpg

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