Innate Immune Mechanisms of Thermogenesis

生热的先天免疫机制

• 批准号: 9551982
• 负责人: Biao Wang
• 金额: $ 44.9万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-25 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9551982
• 关键词: Address; Adipocytes; Adipose tissue; Adult; Alternative Splicing; Behavioral; Binding; Bioenergetics; Biogenesis; Body Temperature; Body Weight; Brown Fat; Cell Respiration; Cells; Chronic; Chronic Disease; Coronary Arteriosclerosis; Coupled; Data; Development; Electron Transport; Embryo; Energy Intake; Energy Metabolism; Epidemic; Fatty Liver; Fatty acid glycerol esters; Genetic; Genomics; Growth; Human; Immune; Immune signaling; Immunity; Immunology; Interleukin-13; Interleukin-4; Knock-out; Knowledge; Laboratories; Licensing; Light; Liver diseases; Lymphoid Cell; Maintenance; Malignant Neoplasms; Mammals; Mediating; Metabolic syndrome; Metabolism; Methods; Mitochondria; Mitochondrial Proteins; Molecular; Mus; Neurodegenerative Disorders; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oxidative Phosphorylation; Paper; Pathway interactions; Perinatal; Physiological; Play; Process; Publishing; Receptor Signaling; Regulation; Reporting; Respiration; Risk Factors; Role; Signal Pathway; Signal Transduction; Skeletal Muscle; Supraclavicular; Techniques; Testing; Thermogenesis; Tissues; Work; adipocyte differentiation; base; combat; cytokine; eosinophil; insight; interest; macrophage; neonate; novel; programs; protein expression; receptor; respiratory; response; therapeutic target; uncoupling protein 1

Project Summary/Abstract Obesity, which results from prolonged imbalance between energy intake and energy expenditure, is an independent risk factor for a number of chronic diseases, including type 2 diabetes, coronary artery disease, fatty liver disease, neurodegenerative disorders, and a number of cancers. Simplistically, there are two major ways of combating obesity: to decrease energy intake or to increase energy expenditure. The recent discovery of cold-induced brown/beige fat in humans has generated a great deal of excitement for its therapeutic targeting in humans. However, our current knowledge of the signaling pathways that license thermogenesis in brown/beige adipose tissue is very limited. This application builds on our new discoveries that immune signals license the thermogenic programs in brown adipose tissue of mice. We will utilize techniques from mouse genetics, immunology, genomics, and metabolism to dissect the underlying mechanisms by which immune signals regulate thermogenesis in brown adipose tissue. The three specific questions we will address are: 1) What are the physiologic mechanisms by which immune signals license thermogenesis in brown adipocytes?, 2) What are the cellular signaling pathways by which immunity regulates uncoupled respiration in brown adipocytes?, and 3) How do immune signals regulate mitochondrial protein expression and respiration? The successful completion of these aims will provide novel insights into cellular and molecular pathways that regulate brown fat thermogenesis, thus advancing our understanding of how to therapeutically target this tissue for the treatment of human obesity and type 2 diabetes.

项目总结/摘要 肥胖是由于能量摄入和能量消耗之间的长期不平衡造成的， 许多慢性疾病的独立危险因素，包括2型糖尿病，冠状动脉疾病， 脂肪肝疾病、神经退行性疾病和许多癌症。简单地说，有两个主要的 对抗肥胖的方法：减少能量摄入或增加能量消耗。最近发现 在人类中，冷诱导的棕色/米色脂肪的产生产生了很大的兴奋，其治疗 以人类为目标然而，我们目前的知识，信号通路许可产热在 棕色/米色脂肪组织非常有限。 这个应用程序建立在我们的新发现上，即免疫信号许可棕色中的产热程序 小鼠的脂肪组织。我们将利用小鼠遗传学、免疫学、基因组学和 代谢，剖析免疫信号调节棕色产热的潜在机制， 脂肪组织我们将解决的三个具体问题是：1） 哪些免疫信号允许棕色脂肪细胞产热？2)细胞信号是什么 免疫调节棕色脂肪细胞非偶联呼吸的途径？（3）如何免疫 信号调节线粒体蛋白表达和呼吸？这些目标的成功实现将 为调节棕色脂肪产热的细胞和分子途径提供了新的见解， 推进我们对如何治疗性靶向该组织以治疗人类肥胖症的理解， 2型糖尿病