The role of adipose tissue in adaptive responses to exercise

项目概要/摘要 脂肪组织表型和生理学被认为是整体代谢健康的重要贡献者， 我们的初步数据表明，运动训练可以改善脂肪组织生物学。的目标 建议的项目是阐明如何改变脂肪组织细胞组成和内分泌信号 可能有助于对运动的有益适应，并产生对作用的新的机械见解。 脂肪组织在代谢健康中的作用。 目的1研究运动训练对脂肪组织巨噬细胞数量和炎症反应的影响。 并将研究这些变化与代谢健康的关联。老年糖尿病前期患者 肥胖者将参加为期3个月的运动训练干预， 巨噬细胞群和脂肪炎性分子标记在训练前后测量 干预目标2将确定急性运动如何触发关键信号事件（例如，免疫细胞浸润， 脂肪组织中的脂肪因子、细胞外囊泡的释放），其可能具有旁分泌和内分泌 方面的影响.将在收集的脂肪组织活检中评估白细胞群和炎症特征 老年人在30分钟的自行车运动之前，之后立即和3小时后。脂肪 将在血浆和从培养的人脂肪组织收集的培养基中评估组织分泌组 外植体总的来说，这个项目将阐明运动对脂肪组织表型的影响，并提供 对代谢功能障碍原因的机械性洞察。 职业发展计划，伴随着拟议的项目将有助于我成功过渡到 独立研究科学家。我的职业发展计划将为我建立一个 独立研究方案，包括以下内容：多学科领域的教学培训; 生物信息学、临床和转化研究、糖尿病、衰老和运动方面的专家指导; 临床研究、生物信息学和科学交流方面的实践经验 发展计划，我将学习新的统计和生物信息学方法和实验室技术;获得 在边缘科学领域的基本知识，使我能够提出综合性的问题，并寻求 多学科合作者;并领导独立的临床试验，获得临床研究的重要经验 在经验导师的指导下由我的导师团队和我的团队所营造的支持性环境， 马约诊所将允许我建立多学科合作，并成为一个独立的调查员。

PROJECT SUMMARY/ABSTRACT Adipose tissue phenotype and physiology are thought to be important contributors to overall metabolic health, and our preliminary data suggests that exercise training improves adipose tissue biology. The objectives of the proposed project are to elucidate how alterations in adipose tissue cellular composition and endocrine signaling may contribute to the beneficial adaptations to exercise and to generate new mechanistic insights into the role of adipose tissue in metabolic health. Aim 1 will study the effects of exercise training on adipose tissue macrophage populations and inflammatory profile and will examine the association of these changes with metabolic health. Older adults with prediabetes and obesity will participate in a 3-month exercise training intervention with metabolic health, adipose tissue macrophage populations, and adipose inflammatory molecular signatures measured before and after the training intervention. Aim 2 will determine how acute exercise triggers key signaling events (e.g., immune cell infiltration, release of adipokines, extracellular vesicles) in adipose tissue that are likely to have paracrine and endocrine effects. Leukocyte populations and inflammatory signatures will be assessed in adipose tissue biopsies collected from older adults before, immediately after, and 3 hours after a 30-minute bout of cycling exercise. The adipose tissue secretome will be assessed in plasma and in media collected from cultured human adipose tissue explants. Overall, this project will elucidate the effects of exercise on adipose tissue phenotype and provide mechanistic insight into the causes of metabolic dysfunction. The career development plan that accompanies the proposed project will facilitate my successful transition to independent research scientist. My career development plan will provide the foundation on which I can build an independent research program, comprising the following elements: didactic training in multidisciplinary fields; mentorship by experts in bioinformatics, clinical and translational research, diabetes, aging, and exercise; and hands-on experience in clinical research, bioinformatics, and scientific communication With the proposed career development plan, I will learn new statistical and bioinformatics approaches and laboratory techniques; gain basic knowledge in tangential fields of science to enable me to ask integrative questions and to seek out multidisciplinary collaborators; and lead an independent clinical trial, gaining vital experience in clinical research with guidance from experience mentors. The supportive environment fostered by my mentorship team and by Mayo Clinic will allow me to establish multidisciplinary collaborations and to become an independent investigator.