Reduction in CVD risk in children by physical activity

通过体力活动降低儿童心血管疾病风险

• 批准号: 7626363
• 负责人: ROBERT C HICKNER
• 金额: $ 29.55万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7626363
• 关键词: 5' -AMP-activated protein kinase; Abdomen; Acetylcholine; Acute; Address; Adipocytes; Adipose tissue; Adolescent; Adult; Aerobic; African American; Age; American; Arts; Blood; Blood Glucose; Blood flow; Body mass index; Cardiovascular Diseases; Caucasians; Caucasoid Race; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Chronic; County; Data; Development; Down-Regulation; Enzymes; Exercise; Exhibits; Fasting; Fatty acid glycerol esters; Future; Gene Expression; Glucose; Glycerol; Health; High Prevalence; Homeostasis; Hour; Human; Hyperglycemia; Hyperinsulinism; Incidence; Individual; Inflammatory; Infusion Pumps; Insulin; Insulin Resistance; Investigation; Laboratory Study; Life; Link; Lipids; Lipolysis; Measures; Mediating; Metabolic; Metabolic syndrome; Metabolism; Methodology; Methods; Microdialysis; Modeling; Monitor; National Health and Nutrition Examination Survey; Nerve; Nitric Oxide; Nitric Oxide Synthase; Norepinephrine; North Carolina; Obesity; Overweight; Physical activity; Plasma; Protein Isoforms; Regulation; Reporting; Research; Rest; Risk; Risk Factors; Risk Marker; Rodent; Role; Solutions; System; Testing; Time; Tissues; Training; Weight Gain; Youth; aged; base; cardiovascular disorder risk; cardiovascular risk factor; caucasian American; cytokine; feeding; group intervention; improved; in vivo; indexing; inhibitor/antagonist; insulin sensitivity; insulin sensitizing drugs; interstitial; macrophage; middle childhood; novel; obesity in children; obesity risk; omega-N-Methylarginine; prevent; programs; response; sedentary; sex; sterol esterase; subcutaneous

DESCRIPTION (provided by applicant): Childhood overweight is a strong predictor of adult obesity. Abnormalities in glucose and lipid homeostasis are associated with body weight gain and many o f the alterations found in the Metabolic Syndrome. Obese sedentary adults, in particular obese African Americans, are more prone to hyperglycemia, hyperinsulinemia, lower rates of post- absorptive adipose tissue lipolysis per unit fat mass, poor post- prandial suppression of lipolysis and reduced blood flow. We propose to implement the novel use of microdialysis to assess interstitial glucose and glycerol concentrations as indices of blood glucose and adipose tissue lipolysis, respectively, and adipose tissue blood flow in lean and obese prepubescent children continuously over 24 hours. The hypothesis is that overweight children exhibit higher interstitial glucose concentrations throughout the day, reduced rates of basal lipolysis and poor postprandial suppression of lipolysis compared to lean children, and that these abnormalities will be associated with a higher prevalence of cardiovascular disease risk factors. Furthermore, 16- weeks of physical activity will normalize, or bring closer to lean, the glucose and lipolytic profiles of overweight children and will result in an improved cardiovascular disease risk profile. We will investigate lean and overweight African American and Caucasian children (8- 10 yr; n=80) before and after 16 weeks of increased physical activity. Subcutaneous abdominal adipose tissue lipolysis and glucose profiles will by monitored using microdialysis under resting fasting and fed conditions as well as in response to exercise. Microdialysis probes will be perfused with either a control solution, an inhibitor of nitric oxide synthase (L- NMMA), or an activator of nitric oxide synthase (acetylcholine) to investigate the mechanism of the proposed reduction of basal lipolysis in obese and African American children. These investigations will determine if acute and chronic aerobic physical activity improves the lipolytic and glucose profiles in lean and overweight children, and whether these beneficial changes will be accompanied by improvements in cardiovascular disease risk factors. The long- term objectives are: 1) to identify the relevant in- vivo metabolic and circulatory parameters that are deficient in overweight children and adults that place them at risk for metabolic and cardiovascular disease; and 2) to find practical means of reversing metabolic and circulatory insufficiencies in obese individuals, thereby reducing the incidence of metabolic and cardiovascular diseases.

描述（由申请人提供）：儿童期超重是成人肥胖的有力预测因素。葡萄糖和脂质稳态的异常与体重增加以及代谢综合征中发现的许多改变有关。肥胖的久坐成年人，特别是肥胖的非洲裔美国人，更容易出现高血糖、高胰岛素血症、每单位脂肪质量吸收后脂肪组织脂解率较低、餐后脂解抑制较差以及血流量减少。我们建议采用微透析的新方法来评估间质葡萄糖和甘油浓度，分别作为血糖和脂肪组织脂解的指标，以及瘦和肥胖青春期前儿童连续24小时内的脂肪组织血流量。该假设认为，与瘦儿童相比，超重儿童全天间质葡萄糖浓度较高，基础脂肪分解率降低，餐后脂肪分解抑制较差，并且这些异常与心血管疾病危险因素的患病率较高有关。此外，16周的体力活动将使超重儿童的葡萄糖和脂肪分解状况正常化或接近瘦身，并改善心血管疾病的风险状况。我们将调查 16 周增加体力活动前后的消瘦和超重非裔美国人和白人儿童（8-10 岁；n=80）。在静息禁食和进食条件下以及对运动的反应下，将使用微透析监测皮下腹部脂肪组织脂肪分解和葡萄糖分布。微透析探针将灌注对照溶液、一氧化氮合酶 (L-NMMA) 抑制剂或一氧化氮合酶激活剂（乙酰胆碱），以研究拟议减少肥胖和非裔美国儿童基础脂肪分解的机制。这些研究将确定急性和慢性有氧体力活动是否可以改善瘦和超重儿童的脂肪分解和血糖状况，以及这些有益的变化是否会伴随着心血管疾病危险因素的改善。长期目标是：1）确定超重儿童和成人缺乏的相关体内代谢和循环参数，这些参数使他们面临代谢和心血管疾病的风险； 2）找到扭转肥胖个体代谢和循环功能不全的实用方法，从而降低代谢和心血管疾病的发病率。