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口肥胖率的迅速上升，目前儿童(6-11岁)和青少年(12-19岁)的肥胖率分别超过18%和17%，而年轻人(20-39岁)的肥胖率接近30%。虽然关于体重调节和肥胖症的发展已经学到了很多，但肥胖率仍在继续上升，这表明即使在今天，预测健康体重保持的因素仍然知之甚少。事实上，从超重的青少年过渡到肥胖的成年人几乎是不可避免的，13岁的儿童成年后肥胖的可能性超过50%，他们的BMI百分位数达到或超过年龄和性别的第95个百分位数。但是，如果我们能够阻止预期的从超重青少年到肥胖成年人的转变，并在年轻人开始感到独立赋予他/她权力的关键时刻对他/她进行干预，会怎么样？这是训练干预和运动反应遗传学(TIGER)研究的精髓。TIGER的研究始于2003年，目的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的人进行定期运动。TIGER研究中的受试者目前接受了30周(两个学期)的运动训练，每周3天，每次40分钟，训练速度是年龄预测最大心率的65-85%。超过80%的受试者体重减轻或保持在2公斤以内，只有18%的受试者增重超过2公斤。在研究的第一阶段，我们已经确定了基因变异和运动中断之间的初步联系，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。我们将集中在三个主要调查领域：1)对TIGER研究干预方案进行正式评估，以实现参与者的长期变化；2)调查骨骼肌和皮下脂肪组织中的基因表达模式，以此作为确定与运动反应相关的基因的策略；以及3)调查遗传变异与运动坚持之间的联系。受试者将根据建立的Tiger方案接受为期35周的运动训练，研究方案完成后6、12和24个月将重新联系受试者，询问他们目前的锻炼习惯和体重。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的遗传因素。最后，将分析运动训练前后皮下脂肪、骨骼肌和外周血白细胞的基因表达模式，以确定影响运动训练所导致的生理变化的因素。这项研究的结果旨在启发我们目前对个人如何反应和/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。 与公共健康相关：在青春期确立的肥胖症强烈预示着肥胖症在成年后的余生，其后果可能是毁灭性的，其特征是终生共同疾病和抑郁症的负担。这项研究将提供一种身体活动的暴露，旨在通过评估这种暴露是否会导致锻炼行为和身体成分的持久变化来教导和赋予久坐的大学年龄的人变得活跃起来。这项研究还将提供更好的理解，了解影响锻炼计划的持久性和影响全身对锻炼的反应的遗传因素。

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.