Real Time Visualization of Obesity-Induced Inflammation in Adipose Tissue

脂肪组织中肥胖引起的炎症的实时可视化

• 批准号: 8174309
• 负责人: Carey N Lumeng
• 金额: $ 19.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-12 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8174309
• 关键词: Address; Adipocytes; Adipose tissue; Adoptive Transfer; Animals; Antigens; Area; B-Lymphocytes; Behavior assessment; Biological Assay; Biology; Blood Vessels; CD4 Positive T Lymphocytes; CD8B1 gene; Cardiovascular Diseases; Cell Communication; Cell physiology; Cells; Chronic; Complement; Confocal Microscopy; Dendritic Cells; Dental crowns; Development; Diabetes Mellitus; Disease; Drug Formulations; Event; Fatty acid glycerol esters; Foundations; Functional disorder; Future; Generations; Goals; Hand; Health; Image; Imagery; Immobilization; Immunity; Immunology; In Situ; Inflammation; Inflammation Mediators; Inflammatory; Insulin Resistance; Interferons; Leukocytes; Life; Light; Link; Lymph; Lymphocyte; Lymphocyte Activation; Lymphoid; Lymphoid Tissue; Maintenance; Measures; Metabolic syndrome; Metabolism; Methodology; Methods; Microscopy; Modeling; Mus; Nature; Non-Insulin-Dependent Diabetes Mellitus; Obese Mice; Obesity; Pathway interactions; Penetration; Perfusion; Play; Property; Reporter; Research; Research Personnel; Resolution; Resources; Role; Signal Transduction; Stem cells; Stromal Cells; Structure; T-Cell Activation; T-Lymphocyte; Techniques; Technology; Testing; Time; Tissues; Visceral; White Blood Cell Count procedure; Work; base; cell motility; cell type; design; interest; intravital microscopy; lymph nodes; macrophage; migration; mouse model; novel; programs; research study; stem cell population; tool; two-photon

DESCRIPTION (provided by applicant): Obesity-induced inflammation plays an important role in the link between obesity and diseases such as cardiovascular disease and type 2 diabetes. The mechanism behind this relates to the wide range leukocytes found in adipose tissue that secrete numerous inflammatory mediators. Since the initial identification of macrophages in fat, the number of leukocyte types present in fat have greatly increased and now include most leukocyte types. Unfortunately, an integrated understanding of how these cells interact with each other and with adipocytes is lacking and limits progress in the field. We feel that this gap in our understanding is due in large part to the limited techniques available to assay inflammatory cells in fat. Furthermore, we feel that there are many dynamic cellular events that are occurring in fat but are not being captured. Therefore, the goal of this study is to design and implement a novel methodology for intravital microscopy on adipose tissue in mouse models of obesity. Being able to observe leukocyte interactions in fat can reveal the mechanisms involved in the initiation and maintenance of inflammation in obesity. This advance will be significant as it has the potential to unlock the mystery of how inflammation is generated in obesity. We will accomplish our goal by completing two aims. (1) To establish the methodology for intravital imaging of leukocytes in adipose tissue. This will employ two-photon confocal microscopy to generate 4D views of fat in live animals. (2) To evaluate the effects of obesity on T cell migration in relation to fat associated lymphoid clusters (FALCs). We will use intravital microscopy to test a model of obesity-induced induction of T cell flux out of FALCs and into fat to generate inflammation. At the end of the project, we hope to generate a new standardized tool for obesity researchers that can generate new models and provide a window into the dynamic properties of adipose tissue stromal cells. PUBLIC HEALTH RELEVANCE: With obesity, adipose tissue dysfunction contributes the development of diseases such as diabetes and metabolic syndrome. This is closely linked to the recruitment and activation of inflammatory cells to fat. Research in this area is currently limited due to few methods that are available to researchers and clinicians to study inflammatory cells in fat. To address this, we will develop a novel resource for obesity researchers to enable visualization of inflammatory cells in live adipose tissue.

描述（由申请人提供）：肥胖引起的炎症在肥胖与心血管疾病、2型糖尿病等疾病之间的联系中起着重要作用。这背后的机制与脂肪组织中广泛存在的白细胞有关，白细胞分泌大量炎症介质。自从最初在脂肪中发现巨噬细胞以来，脂肪中存在的白细胞类型的数量大大增加，现在包括大多数白细胞类型。不幸的是，缺乏对这些细胞如何相互作用以及如何与脂肪细胞相互作用的综合理解，这限制了该领域的进展。我们认为，这种理解上的差距在很大程度上是由于可用于测定脂肪中炎症细胞的技术有限。此外，我们认为有许多动态的细胞事件正在脂肪中发生，但没有被捕获。因此，本研究的目的是设计和实施一种新的方法，用于对肥胖小鼠模型的脂肪组织进行活体显微镜观察。能够观察到白细胞在脂肪中的相互作用，可以揭示肥胖炎症发生和维持的机制。这一进展意义重大，因为它有可能解开肥胖中炎症是如何产生的谜团。我们将通过完成两个目标来实现我们的目标。(1)建立脂肪组织白细胞活体显像方法。这将采用双光子共聚焦显微镜来生成活体动物脂肪的4D视图。(2)评估肥胖对与脂肪相关淋巴细胞簇（FALCs）相关的T细胞迁移的影响。我们将使用活体显微镜来测试肥胖诱导的T细胞流出FALCs并进入脂肪以产生炎症的模型。在项目结束时，我们希望为肥胖研究人员生成一个新的标准化工具，可以生成新的模型，并为脂肪组织基质细胞的动态特性提供一个窗口。