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

打破久坐以抵消久坐行为引起的代谢变化

• 批准号: 8913958
• 负责人: Audrey Bergouignan
• 金额: $ 8.77万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8913958
• 关键词: 1,2-diacylglycerol; Adult; Adverse effects; Award; Behavior; Biochemistry; Biological; Biological Markers; Biometry; Calorimetry; Cardiovascular Diseases; Cause of Death; Cells; Ceramides; Cholesterol; Clinical Research; Collaborations; Complement; Data; Development Plans; Diet; Dietary Fats; Dietary Fatty Acid; Diglycerides; Employee Strikes; Energy Metabolism; Engineering; Ensure; Environment; Equation; Exercise; Fatty acid glycerol esters; Functional disorder; Gene Proteins; Glucose; Goals; Government; Health; Health Benefit; High Density Lipoproteins; Hour; IL6 gene; Individual; Inflammatory; Insulin; Interleukin-10; Interruption; Intervention; Knowledge; Label; Lead; Life; Lipids; Low-Density Lipoproteins; Measures; Mediating; Mentors; Metabolic; Metabolism; Mitochondria; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Overweight; Palmitates; Phase; Physical activity; Physiology; Plasma; Population Study; Public Health; Recommendation; Research; Resolution; Risk; Scientist; Skeletal Muscle; Societies; Techniques; Testing; Time; Tissues; Training; Training Programs; Triglycerides; Water; acylcarnitine; career development; combat; design; evidence base; experience; improved; indexing; innovation; insulin sensitivity; intravenous glucose tolerance test; mortality; multidisciplinary; oxidation; physical conditioning; post-doctoral training; programs; research study; sedentary; trafficking

DESCRIPTION (provided by applicant): 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 fil 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.

描述（由申请人提供）：本提案概述了职业发展计划，以帮助奥黛丽·伯古尼南博士完成博士后培训，并建立一个独立的研究计划，重点是久坐行为的生理病理学。她的培训将在一个多学科的科学家小组中进行，该小组具有肥胖，代谢，全身和线粒体生理学，生物化学和生物统计学的研究专长。她的导师，丹尼尔贝森博士，有一个广泛的经验，与学员，将补充那些在她的咨询团队，博士Reusch，墨菲，梅兰森和潘。总的来说，这个团队将提供一个出色的培训环境，使她能够填补她的工具箱中的关键空白，需要使用从全身到组织，细胞，蛋白质和基因水平的综合方法来研究久坐行为和不良代谢健康结果之间因果关系的机制。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。在该奖项的培训阶段，她将加强她的学术活动，建立重要的合作，并获得关键数据，这将确保她成功过渡到独立。理由：人口研究中有新的证据表明，久坐不动的时间与全因死亡率有关，包括肥胖、2型糖尿病和心血管疾病。重要的是，这些关联与锻炼时间无关。然而，久坐时间的频繁中断与代谢健康结果有益相关，即使在经常锻炼的人中也是如此。我们的假设是，打破长期坐着改善代谢健康。我们的目标是使用综合的方法来了解生物学机制，这些机制是长期久坐的频繁中断与改善代谢健康结果之间联系的基础。设计图：一项24小时的研究将首先确定超重成年人的休息时间延长对全身底物使用和餐后葡萄糖和胰岛素浓度的影响，这是代谢健康的两个核心组成部分。第一项研究将为申请人提供培训经验和初步数据，以进行R00阶段中拟定的更确定性研究。将比较4周微爆发活动与传统热量当量运动训练对血浆心脏代谢标志物（代谢健康指数）的影响。将进一步描述与胰岛素敏感性相关的潜在机制，即全身底物使用、膳食脂肪氧化和骨骼肌脂质组分的运输以及线粒体功能。相关性：我们相信，拟议中的研究将为打破长时间坐着与短时间活动的健康益处提供初步证据基础。这种创新的策略可能比传统的方法更有效地对抗久坐行为的不良影响。