Exercise regulation of glucose homeostasis

运动调节葡萄糖稳态

• 批准号: 10304134
• 负责人: LAURIE J GOODYEAR
• 金额: $ 65.45万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-16 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304134
• 关键词: Adult Children; Award; Breeding; Code; DNA; Data; Diabetes Mellitus; Diabetes prevention; Diet; Environmental Risk Factor; Epidemiology; Epigenetic Process; Exercise; Fathers; Fatty acid glycerol esters; Female; Funding; Future Generations; Generations; Goals; Health; Health Benefit; Healthcare; Hepatocyte; High Fat Diet; Impairment; Incidence; Intervention; Investigation; Liver; Mediating; Metabolic; Metabolism; Methods; Modification; Molecular; Mothers; Mus; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Onset of illness; Overnutrition; Parents; Persons; Physical activity; Play; Pregnancy; Research Project Grants; Risk; Risk Factors; Role; Skeletal Muscle; Testing; Tissues; Training; United States; Work; World Health Organization; blood glucose regulation; disease transmission; epigenetic regulation; exercise training; feeding; glucose production; glucose tolerance; glucose uptake; impaired glucose tolerance; improved; insulin sensitivity; liver function; male; maternal obesity; metabolic phenotype; mother nutrition; negative affect; nutrition; obesity development; offspring; prevent; sex

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.

项目摘要/摘要 肥胖和2型糖尿病的发生率正在以惊人的速度升高 世界。定期体育锻炼可以防止或延迟2型糖尿病的发作，至少一部分 这些重要效果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产生有益的影响。现在提出的新兴数据 母亲在怀孕之前和怀孕期间进行的练习可能对 后代健康。虽然众所周知，诸如高脂饮食之类的次优孕妇饮食可能会负面 影响后代健康，孕产妇运动的影响尚未得到很好的探索。来自电流的研究 该奖项的资金周期已经确定，母亲（F0代）锻炼培训可以改善后代 （F1生成）代谢健康，包括葡萄糖耐量和胰岛素敏感性，可以废除 产妇高脂进食对后代代谢健康的有害影响。有趣的是，这些研究发现 父亲运动对后代（F1）代谢健康也有深远的影响，改善了有害的 父亲高脂肪进食对后代葡萄糖耐受性，脂肪质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主要的 介导孕产妇运动对后代健康的有益作用的机制。用于父亲运动， 初步数据表明，对肝脏和肌肉的适应是有益的主要机制 父亲运动对后代健康的影响。未来五年的该项目的重点是 了解这些有益效果的基础机制。也有证据表明有害 不良母体（F0）饮食的影响可以通过多代（F2）传播。是否孕产妇运动 尚不清楚饮食对后代后代（F2）的这些有害影响。总体 该项目的假设是母亲和父亲运动训练可以改善全身和组织 男性和女性后代的代谢和表观遗传修饰介导 锻炼。有三个特定的目的：1）确定孕产妇运动训练的机制 改善F1后代肝脏的代谢表型，2）确定盛大运动的影响 F2代谢健康的培训，3）确定父亲运动训练对F1后代的影响 代谢健康。这些研究可能导致新的范式，从而使母亲和父亲的运动是 被视为促进后代代谢健康的中心，降低了2型糖尿病的风险 几代人。