Intensive Exercise to Improve Mitochondrial Dysfunction in Pediatric Obesity

描述(由申请人提供)： 肥胖症和2型糖尿病正在美国和世界范围内以流行病的速度发生。据估计，全球糖尿病的负担在未来25年将翻一番。肥胖儿童有发生胰岛素抵抗、相对胰岛素缺乏症和2型糖尿病的风险。由于缺乏非侵入性预测性测试、个体风险知识和有效的预防措施，2型糖尿病的预防受到阻碍。越来越多的证据表明，线粒体的改变有助于人类糖尿病的发展。因此，探索线粒体功能障碍作为儿童糖尿病的潜在预测因子和潜在的预防目标是很重要的。拟议方案的目的是确定高强度运动干预是否能改善线粒体功能障碍和胰岛素抵抗的儿童的线粒体功能。非侵入性成像技术的使用将允许在体内对线粒体活动进行功能性评估。我们建议研究一种强化运动方案，旨在改善胰岛素抵抗儿童的线粒体功能，并通过磁共振波谱记录线粒体功能障碍。本研究旨在探讨高危儿童线粒体功能异常的可塑性。总之，拟议的项目将调查线粒体功能作为儿童胰岛素抵抗和2型糖尿病发展的非侵入性预测标记物，并试图通过高强度运动干预来改变线粒体功能。对儿童线粒体功能障碍的研究既可以确定疾病的风险人群，也可以为预防和治疗提供分子治疗靶点。

DESCRIPTION (provided by applicant): Obesity and type 2 diabetes are occurring at epidemic rates in the United States and worldwide. The global burden of diabetes is estimated to double over the next 25 years. Obese children are at risk for the development of insulin resistance, relative insulin deficiency and type 2 diabetes mellitus. The prevention of type 2 DM is hindered by the lack of a non-invasive predictive test, knowledge as to individual risk and effective preventative measures. There is increasing evidence that alterations in mitochondria contribute to the development of diabetes in humans. Therefore, it is important to explore mitochondrial dysfunction as a potential predictor of diabetes in children and a potential target for prevention. The aims of the proposed protocol are to determine whether an intensive exercise intervention can improve mitochondrial function in children identified as having mitochondrial dysfunction and insulin resistance. The use of a non-invasive imaging technique will allow for a functional in vivo assessment of mitochondrial activity. We propose the investigation of an intensive exercise protocol designed to improve mitochondrial function in children who are insulin resistant and have documented mitochodrial dysfunction by magnetic resonance spectroscopy. The study is designed to investigate the plasticity of abnormal mitochondrial function in high risk children. In summary, the proposed projects will investigate mitochondrial function as a non-invasive predictive marker for the development of insulin resistance and type 2 diabetes mellitus in children and attempt to modify mitochondrial function with an intensive exercise intervention. The study of mitochondrial dysfunction in children may both identify those at risk for disease and provide a molecular therapeutic target for prevention and treatment.