Regulation of adipose inflammation and metabolic syndrome by adipsin/factor D

Adipsin/D 因子对脂肪炎症和代谢综合征的调节

• 批准号: 8627232
• 负责人: James C Lo
• 金额: $ 0.11万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-21 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8627232
• 关键词: Address; Adipocytes; Adipose tissue; Advisory Committees; Alternative Complement Pathway; Anaphylatoxins; Area; Biochemical; Biological Assay; Biology; Blood Vessels; Cardiology; Cardiovascular Diseases; Cells; Cellular biology; Clinical; Complement 3a; Complement Factor D; Dana-Farber Cancer Institute; Data; Developed Countries; Development; Development Plans; Diabetes Mellitus; Diet; Disease; Doctor of Medicine; Doctor of Philosophy; Environment; Faculty; Flow Cytometry; Functional disorder; Gene Expression; Genetic; Genetic Models; Glucose Intolerance; Health; Homeostasis; Hospitals; Immune; Inflammation; Inflammatory; Israel; K-Series Research Career Programs; Knockout Mice; Link; Malignant Neoplasms; Medical center; Medicine; Mentors; Mentorship; Metabolic; Metabolic Diseases; Metabolic syndrome; Modeling; Molecular; Mus; Obesity; Pathogenesis; Pathway interactions; Play; Positioning Attribute; Prevalence; Principal Investigator; Public Health Schools; Recombinant Proteins; Regulation; Research Personnel; Research Proposals; Risk Factors; Role; Scientist; Stress; Testing; Tissues; Transgenic Mice; Transgenic Organisms; United States National Academy of Sciences; Woman; adipsin; blood glucose regulation; career development; chemokine; cytokine; diabetic; effective therapy; improved; in vivo; lipid metabolism; macrophage; medical schools; member; metabolic abnormality assessment; mortality; novel; novel therapeutic intervention; obesity treatment; professor; research study; restoration; tool; trend

DESCRIPTION (provided by applicant): This research proposal outlines a 5-year career development plan for James C. Lo, M.D., Ph.D., cardiology fellow at Brigham and Women's Hospital and Harvard Medical School to achieve independence as a principal investigator under the mentorship of Bruce Spiegelman, Ph.D., Professor of Cell Biology and Medicine at the Dana-Farber Cancer and Harvard Medical School. Dr. Spiegelman is a member of the National Academy of Sciences and a world expert on adipose biology and metabolic diseases. Importantly, Dr. Spiegelman has a strong track record of mentoring scientists with over 20 trainees holding academic faculty positions. An advisory committee composed of G¿khan Hotamisligil, M.D, Ph.D. Professor at the Harvard School of Public Health, Diane Mathis, Ph.D. Professor at Harvard Medical School, and Evan Rosen, M.D., Ph.D. Associate Professor at Beth Israel Deaconess Medical Center will provide expertise on energy homeostasis, inflammation, stress, lipid metabolism, adipocyte lineage commitment/differentiation, and immune regulation. Dr. Lo will take advantage of the world class environment at the Spiegelman lab and surrounding Harvard Medical School campus, including the Dana-Farber Cancer Institute and Brigham and Women's Hospital to achieve the aims in the proposal. This plan allows Dr. Lo to develop expertise at the intersection of metabolic and inflammatory diseases and transition to an independent investigator. Obesity is an independent risk factor for cardiovascular disease. Recent studies have highlighted the intimate link between adipose tissue inflammation and metabolic diseases. Adipose inflammation drives the development of metabolic syndrome. Adipsin/complement factor D is an adipose-specific immune factor deficient in multiple models of obesity. Adipsin controls the rate-limiting step in the alternative complement pathway and generates the anaphylatoxin C3a, a potent immune activator. This places adipsin as a prime candidate to coordinate adipose tissue inflammation and the ensuing metabolic consequences of obesity and inflammation. The major objective of this project is to determine the function of adipsin in the pathogenesis of obesity and diabetes and to test whether adipsin-directed therapy can be an effective treatment for metabolic disease. The investigator will employ adipsin-deficient mice for in vivo metabolic studies, recombinant proteins within the adipsin pathway to dissect the mechanism, and test novel adipsin-directed therapies for treatment of obesity and diabetes.

描述（由申请人提供）：本研究计划概述了布莱根妇女医院和哈佛医学院心脏病学研究员 James C. Lo（医学博士、哲学博士）的 5 年职业发展计划，以实现作为首席研究员的独立性得到丹纳—法伯癌症研究所和哈佛医学院细胞生物学和医学教授 Bruce Spiegelman 博士的指导。 Spiegelman 博士是美国国家科学院院士和世界级专家。重要的是，Spiegelman 博士在指导科学家方面拥有良好的记录，拥有 20 多名担任学术职务的学员。哈佛公共卫生学院教授 khan Hotamisligil 博士、哈佛医学院博士教授 Diane Mathis 和贝斯以色列女执事医疗中心医学博士、博士副教授提供能量稳态、炎症、压力、脂质代谢、脂肪细胞谱系定型/分化和免疫调节方面的专业知识。Lo 博士将利用 Spiegelman 实验室和哈佛医学院周边的世界一流环境。学校校园，包括达纳法伯癌症研究所和布莱根妇女医院，以实现该计划中的目标，使卢博士能够发展代谢和炎症疾病领域的专业知识，并成为一名独立的肥胖研究人员。最近的研究强调了脂肪组织炎症与代谢疾病之间的密切联系，脂肪素/补体因子 D 是多种模型中缺乏的脂肪特异性免疫因子。 Adipsin 控制替代方案中的限速步骤。 补体途径并产生过敏毒素 C3a，这是一种有效的免疫激活剂，这使得 adipsin 成为协调脂肪组织炎症以及随之而来的肥胖和炎症代谢后果的主要候选者。肥胖和糖尿病的发病机制，并测试adipsin导向疗法是否可以有效治疗代谢疾病，研究人员将使用adipsin缺陷小鼠进行体内代谢研究， Adipsin 途径中的重组蛋白剖析其机制，并测试用于治疗肥胖和糖尿病的新型 Adipsin 导向疗法。