The role of adipose tissue in adaptive responses to exercise

项目总结/文摘

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.