Exercise regulation of glucose homeostasis

项目摘要/摘要 肥胖率和2型糖尿病的发病率在美国和整个国家都在以惊人的速度增长 整个世界。有规律的体力活动可以预防或延缓2型糖尿病的发病，而且至少有一部分 运动的这些重要作用的机制是它对全身和组织的有益作用 葡萄糖动态平衡。这个项目的长期目标是了解分子机制 运动对血糖稳态和新陈代谢健康有好处。现在出现的数据表明 母亲在怀孕前和怀孕期间进行的锻炼可以对 后代健康。虽然已经知道，不理想的母亲饮食，如高脂肪饮食，可能会产生负面影响 在影响子代健康的问题上，母亲运动的影响还没有得到很好的研究。从现在开始的研究 该奖项的资金周期确立了母亲(F0代)运动训练改善后代 (F1代)代谢健康，包括糖耐量和胰岛素敏感性，并可取消 母体高脂喂养对子代代谢健康的不利影响。有趣的是，这些研究发现 父亲的锻炼对后代(F1)的新陈代谢健康也有深远的影响，可以改善有害的 父亲高脂喂养对子代糖耐量、脂肪量和肝细胞血糖的影响 制作。小鼠研究表明，肝脏代谢功能的改善似乎是一个主要原因 母体运动对子代健康有益影响的机制。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 父性锻炼对子代健康的影响。这一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，有害的 不良母亲饮食(F0)的影响可以通过多代传播(F2)。母体锻炼是否 能否逆转饮食对后代后代(F2)的这些有害影响尚不清楚。整体而言 该项目的假设是，母亲和父亲的运动训练可以改善全身和组织 雄性和雌性后代的代谢以及表观遗传修饰介导了这些重要的影响 锻炼身体。有三个具体目标：1)确定产妇运动训练的机制 改善F1子代肝脏代谢表型，2)确定大母体运动的效果 F2代谢性健康训练，3)确定父性运动训练对F1后代的影响 新陈代谢健康。这些研究可能导致一种新的范式，即母亲和父亲的锻炼 被视为促进后代代谢健康的核心，降低未来患2型糖尿病的风险 几代人。

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.