Mitochondrial Function in Pediatric Obesity

小儿肥胖中的线粒体功能

• 批准号: 7874695
• 负责人: Amy Debra Fleischman
• 金额: $ 13.55万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-20 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7874695
• 关键词: Adult; Age; Age-Years; Animals; Area; Body Composition; Cessation of life; Child; Childhood; Chronic; Clinical Data; Clinical Investigator; Cohort Studies; Complications of Diabetes Mellitus; Data; Detection; Development; Diabetes Mellitus; Diagnosis; Environment; Environmental Risk Factor; Epidemic; Etiology; Evaluation; First Degree Relative; Genetic; Hormones; Human; Image; Imaging Techniques; Individual; Insulin; Insulin Resistance; Investigation; Knowledge; Label; Link; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mentorship; Methods; Mitochondria; Molecular Target; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Population; Prevalence; Prevention; Preventive Intervention; Protocols documentation; Puberty; Relative (related person); Research Proposals; Risk; Role; Series; Staging; Technology; Testing; Time; United States; base; career development; cohort; design; diabetic patient; disorder risk; emerging adult; glucose metabolism; high risk; impaired glucose tolerance; in vivo; interest; longitudinal design; mitochondrial dysfunction; novel; predictive modeling; prepuberty; prospective; young adult

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. Although obesity is known to correlate with insulin resistance and diabetes, there is limited knowledge as to causality and mechanism. The level of obesity does not directly predict the level of insulin resistance, and not all insulin resistant individuals will progress to diabetes. Therefore, the cause of insulin resistance is an area of intense scientific interest. There is increasing evidence that alterations in mitochondria contribute to the development of diabetes in humans. The strength of these data provides support for the exploration of mitochondrial function in individuals at risk for the development of diabetes. Pediatric type 2 diabetes is increasing at unprecedented rates. Obese children are at risk for the development of insulin resistance, relative insulin deficiency and type 2 diabetes mellitus. There are currently no accurate predictive models to evaluate which children will develop this chronic debilitating illness. Therefore, it is important to explore mitochondrial dysfunction as a potential predictor of diabetes in children. The aims of the proposed protocol are to explore mitochondrial function in children with obesity compared to healthy control children. The use of a novel non-invasive imaging technique will allow for a functional in vivo assessment of mitochondrial activity. The cross-sectional and subsequent longitudinal design will investigate the contribution of alterations in age, body composition, and pubertal status to the development of insulin resistance and the relationship to mitochondrial dysfunction. The strength of the candidate's background, mentorship and institutional commitment provide a uniquely well suited environment to conduct this research proposal and to support the career development of an independent pediatric clinical investigator in the area of childhood insulin resistance and diabetes. In summary, the proposed project will investigate mitochondrial function, using MRI based technology, as a non-invasive predictive marker for the development of insulin resistance and type 2 diabetes mellitus in children. The study of mitochondrial dysfunction in children may both identify those at risk for disease and provide a molecular target for prevention and treatment.

描述（由申请人提供）：肥胖和2型糖尿病在美国和全球范围内以流行率发生。在未来25年中，糖尿病的全球负担估计是一倍。尽管已知肥胖与胰岛素抵抗和糖尿病相关，但关于因果关系和机制的知识有限。肥胖水平不能直接预测胰岛素抵抗的水平，而并非所有抗胰岛素耐药的个体都会发展为糖尿病。因此，胰岛素抵抗的原因是一个强烈的科学意义的领域。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。这些数据的强度为探索糖尿病风险的个体中线粒体功能的探索提供了支持。小儿2型糖尿病以前所未有的速度增加。肥胖儿童有胰岛素抵抗，相对胰岛素缺乏和2型糖尿病的风险。目前尚无准确的预测模型来评估哪些儿童将发展这种长期使人衰弱的疾病。因此，重要的是要探索线粒体功能障碍作为儿童糖尿病的潜在预测因子。与健康对照儿童相比，该方案的目的是探索肥胖儿童的线粒体功能。新型的非侵入成像技术的使用将允许对线粒体活性进行功能性评估。横截面和随后的纵向设计将研究年龄，身体成分和青春期状态对胰岛素抵抗发展的贡献以及与线粒体功能障碍的关系。候选人背景，指导和机构承诺的优势为进行这项研究建议提供了一个非常适合的环境，并支持儿童胰岛素抵抗和糖尿病领域的独立儿科临床研究者的职业发展。 总而言之，拟议的项目将使用基于MRI的技术来研究线粒体功能，作为儿童胰岛素抵抗和2型糖尿病的非侵入性预测标记。儿童线粒体功能障碍的研究既可以识别出患有疾病风险的人，又可以提供预防和治疗的分子靶标。