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

该提案概述了职业发展计划，以帮助博士奥黛丽Bergouignan完成她的 博士后培训，并建立一个独立的研究计划，重点是生理病理学的 久坐不动的行为她的培训将在一个多学科的科学家小组进行， 肥胖、新陈代谢、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，博士丹尼尔贝塞森，有一个与学员，将补充丰富的经验， 她的顾问团队中的Reusch博士、Murphy博士、Melanson博士和Pan博士。总的来说，这个团队将提供一个 出色的培训环境，这将使她能够填补她的工具箱中的关键空白， 从整体到组织、细胞、蛋白质和基因水平的综合方法来研究机制 这是久坐行为和不良代谢健康结果之间因果关系的基础。 该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：人口研究中有新的证据表明，久坐不动的时间是 与包括肥胖、2型糖尿病和心血管疾病在内的全因死亡率相关。 重要的是，这些关联与运动时间无关。频繁中断， 然而，即使在个体中，久坐时间也与代谢健康结果有益相关 经常锻炼的人我们的假设是，打破长期坐着改善代谢健康。我们 我们的目标是使用综合方法来理解生物学机制，这些机制是 经常中断久坐，改善代谢健康结果。 设计：一项24小时的研究将首先确定超重成人的影响，打破了长期坐着 对全身底物使用和餐后葡萄糖和胰岛素浓度的影响， 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， 在R00阶段进行更确定的研究。4周的微暴流的影响 活动将与传统的热量当量运动训练进行比较， 代谢健康指标潜在机制，即全身底物使用、膳食脂肪 骨骼肌脂质组分和线粒体功能的氧化和运输将进一步被研究。 与胰岛素敏感性相关。 相关性：我们认为，拟议的研究将为健康提供初步的证据基础。 用短时间的活动打破长时间的坐着的好处。这一创新战略可能会更 在对抗久坐行为的不良影响方面比传统方法更有效。

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.