Exercise regulation of glucose homeostasis

项目总结/摘要 肥胖和2型糖尿病的发病率在美国和全世界以惊人的速度增长。 世界有规律的体力活动可以预防或推迟2型糖尿病的发病，至少部分原因是 运动的这些重要作用的机制是它对整个身体和组织的有益作用 葡萄糖稳态该项目的长期目标是了解分子机制， 运动对葡萄糖稳态和代谢健康发挥有益的作用。新数据显示 母亲在怀孕前和怀孕期间进行的锻炼对健康有重要的有益影响， 后代健康虽然已经知道，不理想的母体饮食，如高脂肪饮食， 影响后代的健康，母亲锻炼的影响还没有得到很好的探讨。从目前的研究 该奖项的资助周期已经确定，母体（F0代）运动训练可以改善后代 (F1代）代谢健康，包括葡萄糖耐量和胰岛素敏感性，并可以消除 母体高脂肪喂养对后代代谢健康的有害影响。有趣的是，这些研究发现， 父亲的锻炼也对后代（F1）的代谢健康有深远的影响，改善了有害的 父亲高脂肪喂养对后代糖耐量、脂肪量和肝细胞葡萄糖的影响 生产小鼠研究表明，改善肝脏的代谢功能似乎是一个主要的 机制介导的有益影响，母亲锻炼对后代的健康。作为父亲的锻炼， 初步数据表明，对肝脏和肌肉的适应是有益的主要机制。 父亲锻炼对后代健康的影响。该项目未来五年的重点是 了解这些有益效果背后的机制。也有证据表明， 不良母体（F0）饮食的影响可以通过多代（F2）传播。是否产妇锻炼 能否逆转这些饮食对后代（F2）的不利影响尚不清楚。整体 该项目的假设是，母亲和父亲的运动训练改善全身和组织 研究表明，表观遗传修饰介导了雄性和雌性后代的代谢， 锻炼的有三个具体目标：1）确定产妇运动训练的机制， 改善F1代肝脏代谢表型; 2）确定祖母级运动的影响 3）确定父亲运动训练对F1后代代谢健康的影响 代谢健康这些研究可能会导致一个新的范例，即母亲和父亲的运动是 被视为促进后代代谢健康、降低未来患2型糖尿病风险的核心 代

PROJECT SUMMARY/ABSTRACT The rates of obesity and type 2 diabetes are increasing at alarming rates in the United States and throughout the world. Regular physical activity can prevent or delay the onset of type 2 diabetes, and at least part of the mechanism for these important effects of exercise is the beneficial role it plays on whole body and tissue glucose homeostasis. The long-term goal of this project is to understand the molecular mechanisms by which exercise exerts beneficial effects on glucose homeostasis and metabolic health. Emerging data now suggest that exercise performed by mothers before and during pregnancy can have important beneficial effects on offspring health. While it has been known that suboptimal maternal diets, such as a high fat diet, can negatively affect offspring health, the effects of maternal exercise have not been well explored. Studies from the current funding cycle of this award have established that maternal (F0 generation) exercise training improves offspring (F1 generation) metabolic health, including glucose tolerance and insulin sensitivity, and can abolish the detrimental effects of maternal high fat feeding on offspring metabolic health. Interestingly, these studies found that paternal exercise also has profound effects on offspring (F1) metabolic health, ameliorating the detrimental effects of paternal high fat feeding on offspring glucose tolerance, fat mass, and hepatocyte glucose production. Mouse studies have shown that improved metabolic function of the liver appears to be a major mechanism mediating the beneficial effects of maternal exercise on offspring health. For paternal exercise, preliminary data suggest that adaptations to both liver and muscle are major mechanisms for the beneficial effects of paternal exercise on offspring health. The focus of this project for the coming five years is to understand the mechanisms underlying these beneficial effects. There is also evidence that the detrimental effects of poor maternal (F0) diet can propagate through multiple generations (F2). Whether maternal exercise can reverse these detrimental effects of diet on later generations of offspring (F2) is not known. The overall hypothesis of this project is that maternal and paternal exercise training improves whole-body and tissue metabolism in male and female offspring and that epigenetic modifications mediate these important effects of exercise. There are three specific aims: 1) To determine the mechanisms by which maternal exercise training improves the metabolic phenotype of F1 offspring liver, 2) To determine the effects of grand-maternal exercise training on F2 metabolic health, 3) To determine the effects of paternal exercise training on F1 offspring metabolic health. These studies could result in a new paradigm whereby maternal and paternal exercise are viewed as central in promoting the metabolic health of offspring, reducing the risk of type 2 diabetes in future generations.