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

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的 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，有助于 胰岛素抵抗、2型糖尿病和其他代谢紊乱。据估计，脂肪细胞分泌 超过1,000种多肽和微蛋白，甚至大量的小分子代谢物。的 大多数脂肪细胞分泌组尚未被定义或表征， 知识是这个合作的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鉴定循环蛋白质和代谢物， 细胞起源，并阐明其功能。基于令人信服的初步数据和关键创新 作为这个团队的成员，我们将在2010年创建第一个白色和棕色脂肪细胞分泌组的百科全书。 小鼠模型和人类。具体而言，我们将（1）建立一个小鼠分泌组的百科全书， （2）表征脂肪细胞分泌组对生理应激和病理应激的反应。 状态，（3）表征人体脂肪分泌物组，（4）表征脂肪细胞的功能 分泌蛋白这些从基础生物学到人类研究的研究只有在 通过优化不同学科及其交叉点内的工具。该项目有可能解决 NIDDK的使命的核心问题，如肥胖和肥胖之间联系的分子基础， 2型糖尿病和了解棕色脂肪的抗糖尿病益处是否通过分泌的 调解员我们的研究有可能确定新的分泌介质与肥胖的作用，2型 糖尿病和代谢疾病，促进新技术的发展，提供一个至关重要的新的 研究人员和临床医生的资源，并导致新的生物标志物和治疗。

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.