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.

项目总结/文摘