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

• 批准号: 10907127
• 负责人: Brian T Chait
• 金额: $ 35万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 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/10907127
• 关键词: Abdomen; Address; Adipocytes; Adipose tissue; Antidiabetic Drugs; Area; Bioenergetics; Biological; Biological Markers; Biological Process; Biology; Biopsy; Blood; Brown Fat; Calories; Cell secretion; 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; Link; Longevity; Mass Spectrum Analysis; Mediator; 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; Protein Secretion; Proteins; Research Personnel; Research Project Grants; Research Proposals; Resistance; Resources; Role; Secretory Cell; Signal Transduction; Signaling Molecule; Site; Source; Stress; System; Techniques; Technology; Testing; Therapeutic; 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; response; sedentary lifestyle; small molecule; subcutaneous; thermal stress; tool; Abdomen; Address; Adipocytes; Adipose tissue; Antidiabetic Drugs; Area; Bioenergetics; Biological; Biological Markers; Biological Process; Biology; Biopsy; Blood; Brown Fat; Calories; Cell secretion; 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; Link; Longevity; Mass Spectrum Analysis; Mediator; 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; Protein Secretion; Proteins; Research Personnel; Research Project Grants; Research Proposals; Resistance; Resources; Role; Secretory Cell; Signal Transduction; Signaling Molecule; Site; Source; Stress; System; Techniques; Technology; Testing; Therapeutic; 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; response; sedentary lifestyle; small molecule; subcutaneous; thermal stress; tool

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.

白色和棕色的脂肪细胞不仅在储能和燃烧中起着核心作用，而且还在 产生信号分子的动态分泌细胞，将能量存储的水平连接到其他重要 生理系统。肥胖症中发生的脂肪细胞信号传导特性的破坏有助于 胰岛素抵抗，2型糖尿病和其他代谢疾病。据估计脂肪细胞分泌 超过1,000多种多肽和微蛋白，甚至大量的小分子代谢物。这 绝大多数脂肪细胞分泌组尚未定义或表征，并解决了这一差距 知识是这个合作，跨学科团队项目的主要目标。一个主要的障碍是 缺乏适当的技术来定量识别循环蛋白和代谢物，确定它们 细胞来源并阐明其功能。以引人注目的初步数据和关键创新为基础 这个团队的成员，我们将生成第一个白色和棕色脂肪细胞分泌的百科全书 鼠标模型和人类。具体来说，我们将（1）生成鼠分泌的百科全书 脂肪细胞，（2）响应生理压力和病理学来表征脂肪细胞分泌组 状态，（3）表征人类的脂肪分泌组，（4）表征脂肪细胞的功能 秘密。这些研究跨越了基本生物学到人类学科研究 通过优化不同学科的工具及其交叉点。该项目有可能解决 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益处是否由分泌传达 调解人。我们的研究有可能识别具有肥胖症中作用的新的分泌介体，2型 糖尿病和代谢疾病，催化新技术的发展，提供了至关重要的新技术 研究人员和临床医生的资源，并导致新的生物标志物和疗法。