Breaking-up sitting to offset sedentary behaviors-induced metabolic alterations

项目摘要/摘要 这份提案概述了一项职业发展计划，以帮助奥黛丽·贝古伊尼昂博士完成她的 博士后培训，并建立一个独立的研究计划，专注于 久坐的行为。她的培训将在一个由多学科科学家组成的研究小组中进行 在肥胖、代谢、全身和线粒体生理学、生物化学和生物统计学方面的专业知识。 她的导师Daniel Bessesen博士对学员有丰富的经验，并将得到以下补充 她的顾问团队中的那些人，RRS Reusch，Murphy，Melanson和潘。总体而言，这个团队将提供一个 出色的培训环境，使她能够填补工具箱中使用 从整体到组织、细胞、蛋白质和基因水平的综合机制研究 久坐行为与不良代谢健康后果之间的因果关系。 这一奖项还将巩固她在生物统计学方面的知识和进行临床研究研究的能力。 在这个奖项的培训阶段，她将加强她的学术活动，建立重要的 合作，并获得关键数据，以确保她成功过渡到独立。 理性：人口研究中新出现的证据表明，久坐行为的时间 与各种原因的死亡有关，包括肥胖、2型糖尿病和心血管疾病。 重要的是，这些联系与锻炼时间无关。频繁地中断到 然而，久坐时间有益于新陈代谢健康结果，即使在个人中也是如此 经常锻炼的人。我们的假设是，长时间久坐可以改善新陈代谢健康。我们的 目标是使用综合的方法来理解基础的生物学机制。 经常中断长时间坐着会改善新陈代谢健康状况。 设计：一项24小时的研究将首先确定超重成年人长时间坐着分手的影响 关于全身底物的使用以及餐后血糖和胰岛素浓度，这两个核心成分 新陈代谢健康。第一项研究将为申请人提供培训经验和初步数据，以 执行R00阶段中提出的更明确的研究。4周的微暴效应 活动量与传统热量当量运动训练对血浆心脏代谢的影响比较 标记物，代谢健康指数。潜在的机制，即全身底物的使用，饮食脂肪 骨骼肌脂组分和线粒体功能的氧化和运输将进一步 描述为与胰岛素敏感性有关。 相关性：我们相信，拟议的研究将为健康提供初步的证据基础 打破久坐不动、短时间活动的好处。这一创新战略可能会 与更传统的方法相比，在对抗久坐行为的不利影响方面更有效。

PROJECT SUMMARY / ABSTRACT This proposal outlines a career development plan to help Dr. Audrey Bergouignan complete her postdoctoral training and establish an independent research program focused on the physiopathology of sedentary behaviors. Her training will be conducted in a multidisciplinary group of scientists with research expertise in obesity, metabolism, whole-body and mitochondrial physiology, biochemistry and biostatistics. Her mentor, Dr. Daniel Bessesen, has an extensive experience with trainees that will be complemented by those in her advisory team, Drs Reusch, Murphy, Melanson and Pan. Collectively, this team will provide an outstanding training environment that will allow her to fill critical gaps in her toolbox needed to use an integrative approach from whole-body to tissue, cell, protein and gene levels to study mechanisms underlying the causal relationship between sedentary behaviors and adverse metabolic health outcomes. This award will also solidify her knowledge in biostatistics and ability to conduct clinical research studies. During the training phase of this award, she will strengthen her scholarly activities, establish important collaborations, and acquire critical data that will ensure her successful transition to independence. Rational: There is emerging evidence from population studies that time spent in sedentary behaviors is associated with all-cause mortality including obesity, type 2 diabetes, and cardiovascular diseases. Importantly, these associations are independent of time spent in exercise. Frequent interruptions to sedentary time are however beneficially associated with metabolic health outcomes, even in individuals who exercise regularly. Our hypothesis is that breaking-up prolonged sitting improves metabolic health. Our goal is to use integrative approach to understand the biological mechanisms that underlie associations of frequent interruptions of prolonged sitting with improved metabolic health outcomes. Design: A 24-hr study will first determine in overweight adults the effects of breaking-up prolonged sitting on whole-body substrate use and postprandial glucose and insulin concentrations, two core components of metabolic health. The first study will provide the applicant with training experiences and preliminary data to perform the more definitive study proposed in the R00 phase. The effects of 4 weeks of microbursts of activity will be compared with traditional caloric equivalent exercise training on plasma cardiometabolic markers, index of metabolic health. The underlying mechanisms, i.e. whole body substrate use, dietary fat oxidation and trafficking in skeletal muscle lipid fractions and mitochondrial function will be further delineated in association with insulin sensitivity. Relevance: We believe that the proposed studies will provide an initial evidence base for the health benefits of breaking up prolonged sitting with short bursts of activity. This innovative strategy may be more effective at combating the adverse effects of sedentary behaviors than more traditional approaches.