Training Interventions and Genetics of Exercise Response (TIGER)

描述（由申请人提供）：当今最大的公共卫生问题之一是儿科人群中肥胖症的迅速增加，儿童（6-11岁）和青少年（12-19岁）中肥胖症的比例分别超过18%和17%，而年轻人（20-39岁）中肥胖症的比例接近30%。虽然已经了解了很多关于体重的调节和肥胖症的发展，肥胖症的患病率继续上升，表明即使在今天，预测健康体重维持的因素仍然知之甚少。事实上，从超重青少年到肥胖成年人的转变几乎是不可避免的，在年龄和性别的BMI指数达到或超过第95百分位数的>13岁的儿童中，成年期肥胖的概率超过50%。但是，如果我们能够阻止从超重青少年到肥胖成年人的预期转变，并在年轻人开始感到独立的关键时刻进行干预，会怎么样？这是训练干预和运动反应遗传学（TIGER）研究的本质。TIGER研究始于2003年，目标是确定影响运动训练生理反应的遗传因素，同时让久坐的大学年龄段人群进行定期运动。TIGER研究中的受试者目前接受了30周（2个学期）的运动训练，每周3天，以年龄预测最大心率的65-85%进行40分钟。超过80%的受试者体重减轻或保持在2 kg以内，只有18%的受试者体重增加超过2 kg。我们已经在研究的第一阶段确定了基因变异和运动辍学之间的初步关联，在TIGER研究的第二阶段，我们将建立在这些观察结果的基础上。我们将重点关注三个主要研究领域：1）正式评估TIGER研究干预方案，以实现参与者的长期变化; 2）研究骨骼肌和皮下脂肪组织中的基因表达模式，作为识别运动反应相关基因的策略; 3）研究遗传变异与运动坚持性之间的关联。受试者将根据既定的TIGER方案接受35周的运动训练，并将在研究方案完成后6、12和24个月再次联系受试者，并询问其当前的运动习惯和体重。此外，还将对与运动行为和神经信号相关的候选基因进行遗传分析，以确定可能影响运动坚持性的遗传因素。最后，皮下脂肪，骨骼肌和外周血白细胞中的基因表达模式将在基线和运动训练后进行分析，以确定影响运动训练后生理变化的因素。这项研究的结果旨在启发我们目前对个人如何以及为什么响应和/或坚持锻炼的理解，最终目标是制定更好，更有效的肥胖干预措施。 公共卫生相关性：在青春期确定的肥胖强烈预示着成年后的肥胖，其后果可能是毁灭性的，其特征是伴随疾病和抑郁症的终身负担。这项研究将提供一种身体活动的接触，旨在通过评估这种接触是否会导致运动行为和身体成分的持久变化，来教导和授权久坐的大学年龄段的个人进行身体活动。这项研究还将提供一个更好的了解遗传因素，影响坚持锻炼计划，并影响全身对运动训练的反应。

DESCRIPTION (provided by applicant): Among the greatest public health concerns today is the rapid rise in obesity in the pediatric population, which now exceeds 18% in children (6-11 y) and 17% in adolescents (12-19 y), while obesity among young adults (20-39 y) approaches 30%. Though much has been learned regarding the regulation of body weight and the development of adiposity, the prevalence of obesity continues to rise, demonstrating that even today the factors that predict healthy weight maintenance remain poorly understood. In fact, the transition from overweight adolescent to obese adult is almost inevitable, with the probability of obesity in adulthood exceeding 50% among children >13 years of age whose BMI percentiles meet or exceed the 95th percentile for age and gender. But what if we could deter the expected transition from overweight adolescent to obese adult and intervene on a young person at a critical time when he/she is beginning to feel empowered by independence? This is the essence of the Training Interventions and Genetics of Exercise Response (TIGER) Study. The TIGER Study began in 2003 with the goal of identifying genetic factors that influence physiologic response to exercise training, while introducing sedentary college age individuals to regular exercise. Subjects in the TIGER Study currently underwent 30 weeks (2 semesters) of exercise training, 3 days per week for 40 minutes at 65-85% of age-predicted maximum heart rate. More than 80% of subjects lost weight or maintained their weight within 2 kg, and only 18% of subjects gained more than 2 kg. We have identified preliminary associations between gene variation and exercise dropout in the first phase of the study, and in phase 2 of the TIGER study, we will build on these observations. We will focus on three primary areas of investigation: 1) formal evaluation of the TIGER Study intervention protocol to achieve long-term change in the participants; 2) investigation of gene expression patterns in skeletal muscle and subcutaneous adipose tissue as a strategy for identifying genes related to exercise response; and 3) investigation of the association between genetic variation and exercise adherence. Subjects will undergo 35 weeks of exercise training based on the established TIGER protocol, and subjects will be re-contacted 6, 12, and 24 months following completion of the study protocol and questioned regarding current exercise habits and body weight. In addition, genetic analysis of candidate genes related to exercise behavior and neural signaling will be undertaken in order to identify genetic factors that may influence exercise adherence. Finally, patterns of gene expression in subcutaneous adipose, skeletal muscle, and peripheral leukocytes will be analyzed at baseline and following exercise training in order to identify factors that influence physiologic change consequent to exercise training. Results from this study are designed to enlighten our current understanding of how and why individuals respond and/or persist in exercise, with the ultimate goal of formulating better and more efficacious interventions for obesity. PUBLIC HEALTH RELEVANCE: Obesity established in adolescence strongly predicts obesity for the remainder of adult life, and the consequences are potentially devastating, characterized by a lifelong burden of co-morbid conditions and depression. This study will provide an exposure to physical activity that is designed to teach and empower sedentary college age individuals to become physically active by evaluating whether such exposure can result in lasting changes in exercise behavior and body composition. The study will also provide a better understanding of the genetic factors that influence persistence in an exercise program and that influence whole body response to exercise training.