An Encyclopedia of the Adipose Tissue Secretome to Identify Mediators of Health and Disease

脂肪组织分泌组百科全书，用于识别健康和疾病的介质

基本信息

批准号：
10445049
负责人：
Brian T Chait
金额：
$ 168.88万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10445049
关键词：
Abdomen Address Adipocytes Adipose tissue Antidiabetic Drugs Area Bioenergetics Biological Biological Markers Biological Process Biology Biopsy Blood Brown Fat Calories Chemicals Complement Data Development Diabetes Mellitus Discipline Disease Encyclopedias Fatty acid glycerol esters Female Food Goals Health Homeostasis Human In Vitro Insulin Insulin Resistance Investigation Knowledge Lead Link Longevity Mass Spectrum Analysis Mediator of activation protein Metabolic Diseases Metabolism Methodology Methods Mission Modernization Molecular Molecular Target Mouse Strains Mus National Institute of Diabetes and Digestive and Kidney Diseases Non-Insulin-Dependent Diabetes Mellitus Nutritional Obesity Organ Outcome Pathogenesis Pathologic Physiological Physiology Play Prevalence Property Proteins Prothrombin Research Personnel Research Project Grants Research Proposals Resistance Resources Role Secretory Cell Signal Transduction Signaling Molecule Site Source Stress System Techniques Technology Testing Therapeutic Time Tissues Triglycerides Type 2 diabetic Visceral cell type human subject in vivo innovation insight male member mouse model new technology novel novel therapeutics obesity treatment polypeptide protein metabolite response sedentary lifestyle small molecule subcutaneous thermal stress tool

项目摘要

White and brown adipocytes not only play a central role in energy storage and combustion, but are also dynamic secretory cells that produce signaling molecules that link levels of energy stores to other vital physiological systems. Disruption of the signaling properties of adipocytes, as occurs in obesity, contributes to insulin resistance, type 2 diabetes, and other metabolic disorders. Fat cells have been estimated to secrete more than 1,000 polypeptides and microproteins and even large number of small molecule metabolites. The great majority of the adipocyte secretome has not been defined or characterized and addressing this gap in knowledge is the main goal of this collaborative, interdisciplinary team project. A major obstacle has been the lack of suitable technologies to quantitatively identify circulating proteins and metabolites, determine their cellular origin, and elucidate their function. Building on compelling preliminary data and key innovations from members of this team, we will generate the first encyclopedia of the white and brown adipocyte secretome in mouse models and humans. Specifically, we will (1) Generate an encyclopedia of the secretome of murine adipocytes, (2) Characterize the adipocyte secretome in response to physiological stress and in pathological states, (3) Characterize the adipose secretome in humans, and (4) Characterize the function of the adipocyte secretome. These studies, which span from basic biology to human subject investigation will only be possible by optimizing tools within diverse disciplines and at their intersection. This project has the potential to address questions central to the mission of the NIDDK such as the molecular basis for the links between obesity and type 2 diabetes and understanding whether the anti-diabetic benefits of brown fat are conveyed by secreted mediators. Our studies have the potential to identify new secreted mediators with roles in obesity, type 2 diabetes and metabolic diseases, catalyze the development of new technologies, provide a crucial new resource for researchers and clinicians, and lead to new biomarkers and therapies.

白色和棕色脂肪细胞不仅在能量储存和燃烧中发挥核心作用，而且还动态分泌细胞产生信号分子，将能量储存水平与其他重要物质联系起来生理系统。脂肪细胞信号传导特性的破坏（如肥胖症中发生的情况）有助于胰岛素抵抗、2 型糖尿病和其他代谢紊乱。据估计，脂肪细胞会分泌超过1000种多肽和微生物蛋白甚至大量小分子代谢物。这绝大多数脂肪细胞分泌组尚未被定义或表征，并解决这一差距知识是这个协作、跨学科团队项目的主要目标。一个主要障碍是缺乏合适的技术来定量识别循环蛋白质和代谢物，确定它们的细胞起源，并阐明其功能。以令人信服的初步数据和关键创新为基础作为这个团队的成员，我们将在小鼠模型和人类。具体来说，我们将（1）生成小鼠分泌蛋白组的百科全书脂肪细胞，(2) 表征脂肪细胞分泌组对生理应激和病理应激的反应指出，(3) 表征人类脂肪分泌组，以及 (4) 表征脂肪细胞的功能分泌体。这些从基础生物学到人类受试者研究的研究只有可能通过优化不同学科内及其交叉点的工具。该项目有潜力解决 NIDDK 使命的核心问题，例如肥胖与肥胖之间联系的分子基础 2 型糖尿病并了解棕色脂肪的抗糖尿病功效是否是通过分泌的调解员。我们的研究有可能识别出在 2 型肥胖中发挥作用的新分泌介质糖尿病和代谢疾病，催化新技术的发展，提供关键的新为研究人员和临床医生提供资源，并带来新的生物标志物和疗法。