Effects of maternal exercise on infant mesenchymal stem cell mitochondrial function, insulin action, and body composition in early infancy

Filip Jevtovic, Donghai Zheng, Alex Claiborne, Ericka M. Biagioni, Breanna L. Wisseman, Polina M. Krassovskaia, David N. Collier, Christy Isler, James E. DeVente, P. Darrell Neufer, Linda E. May
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Abstract

Objective: Rates of pediatric obesity are continuously rising and are likely to translate into a high incidence of metabolic disease later in life. Maternal exercise (ME) has been established as a useful non-pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to infant tissues (e.g., skeletal muscle), and remain involved in mature tissue maintenance. Importantly, these cells maintain metabolic characteristics of an offspring donor and provide a model for the investigation of mechanisms behind infant metabolic health improvements. Methods: We used undifferentiated MSC to investigate if ME affects infant MSC mitochondrial function and insulin action, and if these adaptations are associated with lower infant adiposity. Results: We found that infants from exercising mothers have improvements in MSC insulin signaling are related to higher MSC respiration and fat oxidation, and expression and activation of energy-sensing and redox-sensitive proteins. Further, we found that infants exposed to exercise in utero were seemingly leaner at 1-month of age, with a significant inverse correlation between infant MSC respiration and infant adiposity at 6-months of age. Conclusion: These data suggest that infants from exercising mothers are relatively leaner and this is associated with higher infant MSC mitochondrial respiration, fat use, and insulin action.
母亲运动对婴儿早期间充质干细胞线粒体功能、胰岛素作用和身体成分的影响
目的:小儿肥胖率持续上升,并有可能转化为日后代谢性疾病的高发病率。孕产妇运动(ME)已被认为是一种有效的非药物干预措施,可改善婴儿的代谢健康;然而,这些适应性背后的机理研究仍主要局限于动物模型。婴儿间充质干细胞(MSCs)可产生婴儿组织(如骨骼肌),并继续参与成熟组织的维护。重要的是,这些细胞能保持后代供体的代谢特征,为研究婴儿代谢健康改善背后的机制提供了模型。研究方法我们使用未分化间充质干细胞研究 ME 是否会影响婴儿间充质干细胞线粒体功能和胰岛素作用,以及这些适应性是否与婴儿较低的脂肪率有关。结果:我们发现,运动母亲的婴儿间充质干细胞胰岛素信号转导的改善与间充质干细胞较高的呼吸和脂肪氧化以及能量传感蛋白和氧化还原敏感蛋白的表达和激活有关。此外,我们还发现,在子宫内接受锻炼的婴儿在1个月大时似乎更瘦,婴儿间充质干细胞呼吸与6个月大时的婴儿脂肪含量呈显著的反相关。结论这些数据表明,来自运动母亲的婴儿相对较瘦,这与婴儿间充质干细胞线粒体呼吸、脂肪利用和胰岛素作用较高有关。
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