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

摘要 目前的肥胖症治疗方法在保持长期减肥方面基本上不成功， 表明了对可能稳定改变体重和体重的机制的新见解的巨大需要 组成。对干预/预防计划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，而其他人则不是。在这个项目中，我们将把饮食、心理社会/行为、锻炼 在良好控制的运动干预的背景下，表现和代谢组学数据，以表征 能量平衡的行为表现学(BPEB)。BPEB是复合体的高维表示 能量平衡的行为成分之间的相互作用表现在多个水平上，从饮食摄入量 运动和体力活动对这两种行为的心理社会驱动作用。此外，我们将确定如何 运动训练会影响BPEB的变化，我们将使用高密度基因型和代谢组学数据来 衍生与BPEB相互作用的遗传和代谢途径，以调节和影响体内的变化 高强度有氧运动干预后的质量/成分。在这项建议中，我们将利用 训练干预和运动反应遗传学(TIGER)研究的现有资源和英国 生物库。TIGER研究是对运动反应遗传学的最大研究之一，参与者 都经历了一套严格的、有经验证明的有氧运动训练方案。老虎研究 队列由来自多个种族/民族的3,665名参与者组成，平均体重指数为26.2BMI/6.3公斤/平方米。 全面的行为数据、表型、基因类型和存储样本(DNA、RNA和 血浆)可用于这项拟议的研究，并记录了超过120,000次锻炼 TIGER研究记录了记录的持续时间、强度和模式。参与者还报告说 与进食行为和体力活动相关的心理参数。重要的是，相当大的比例 的参与者在整个研究过程中体重显著减轻，尽管事实是 TIGER并不是一项减肥试验，它为研究饮食的自发变化提供了一个独特的机会 以及锻炼背景下的心理社会因素。我们将使用英国生物库的资源，它已经 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/或与饮食和锻炼相互作用的新途径。 最终决定体重和肥胖的行为。

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.