Using Metabolomics to Define the Behavioral Phenomics of Energy Balance and Exercise Response

摘要 目前的肥胖治疗在维持长期减肥方面基本上是不成功的， 证明了对可能稳定改变体重的机制的新见解的巨大需求， 混合物.对干预/预防方案的反应存在显著的异质性， 减少肥胖的风险和发生，这表明一些人可能对给定的 干预，而其他人则没有。在这个项目中，我们将整合饮食，心理社会/行为，运动 性能和代谢组学数据，在良好控制的运动干预的背景下， 能量平衡行为表型组学（Behavioral Phenomics of Energy Balance，BPEB）BPEB是一个复杂的高维表示 能量平衡的行为成分之间的相互作用，其特征在于多个水平，从饮食摄入 锻炼和身体活动的心理驱动因素。此外，我们将确定如何 运动训练影响BPEB的变化，我们将使用高密度基因型和代谢组学数据， 推导出与BPEB相互作用的遗传和代谢途径，以调节和影响身体的变化 在高强度有氧运动干预后的质量/组成。在本提案中，我们将利用 训练干预和运动反应遗传学（TIGER）研究和英国的现有资源 生物银行TIGER研究是关于运动反应遗传学的最大研究之一，参与者 都经过严格的有氧运动训练，并有详细记录。老虎研究 队列由来自多个种族/民族的3，665名参与者组成，平均BMI为26.2至6.3 kg/m2。 行为数据、表型、基因型和存储样本（DNA、RNA和 血浆）可用于这项拟议的研究，超过120，000个记录的运动课程， 记录的持续时间、强度和模式已记录在TIGER研究中。参与者还报告 与饮食行为和身体活动有关的心理参数。重要的是， 的TIGER参与者在整个研究过程中经历了显著的体重减轻，尽管事实上 TIGER不是一个减肥试验，提供了一个独特的机会来研究饮食的自发变化， 和心理社会因素的影响。我们将利用英国生物银行的资源， 超过500，000名参与者和一系列互补的表型和行为数据，用于验证我们的 调查结果。我们的目标是揭示调节、影响和/或与饮食和运动相互作用的新途径 行为来最终决定体重和肥胖。

ABSTRACT Current treatments for obesity have been largely unsuccessful in maintaining long-term weight loss, demonstrating the tremendous need for new insight into mechanisms that may stably alter body mass and composition. There is significant heterogeneity in response to intervention/prevention programs designed to reduce the risk and occurrence of obesity, suggesting that some individuals may be responsive to a given intervention while others are not. In this project, we will integrate dietary, psychosocial/behavioral, exercise performance, and metabolomics data, within the context of a well-controlled exercise intervention, to characterize the behavioral phenomics of energy balance (BPEB). BPEB is a high dimensional representation of the complex interplay between behavioral components of energy balance characterized at multiple levels, from dietary intake to exercise and physical activity to the psychosocial drivers of both behaviors. In addition, we will determine how exercise training influences change in BPEB, and we will use high density genotype and metabolomic data to derive the genetic and metabolic pathways that interact with BPEB to regulate and influence changes in body mass/composition following a high intensity aerobic exercise intervention. In this proposal, we will leverage the existing resources of the Training Interventions and Genetics of Exercise Response (TIGER) Study and the UK Biobank. The TIGER Study is one of the largest studies of the genetics of exercise response in which participants have undergone a rigorous and empirically-documented aerobic exercise training protocol. The TIGER Study cohort consists of 3,665 participants from multiple racial/ethnic groups, with an average BMI of 26.26.3 kg/m2 . A comprehensive battery of behavioral data, phenotypes, genotypes, and stored samples (DNA, RNA, and plasma) are available to this proposed study, and more than 120,000 recorded exercise sessions with documented duration, intensity, and mode have been recorded in the TIGER Study. Participants also reported psychological parameters related to eating behavior and physical activity. Importantly, a substantial proportion of TIGER participants experienced significant weight loss throughout the course of the study, despite the fact that TIGER was not a weight loss trial, providing a unique opportunity to study spontaneous changes in dietary and psychosocial factors in the context of exercise. We will use the resources of the UK Biobank, which has more than 500,000 participants and a complementary array of phenotype and behavior data, for validation of our findings. Our goal is to reveal new pathways that regulate, influence, and/or interact with diet and exercise behavior to ultimately determine body mass and adiposity.