Innate Immune Mechanisms of Thermogenesis

生热的先天免疫机制

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要肥胖是由于能量摄入和能量消耗之间长期失衡而导致的，这是一种多种慢性疾病的独立危险因素，包括2型糖尿病，冠状动脉疾病，脂肪肝病，神经退行性疾病和许多癌症。简单地说，有两个主要打击肥胖的方式：减少能量摄入或增加能量消耗。最近的发现人类感冒引起的棕色/米色脂肪的治疗引起了极大的兴奋针对人类。但是，我们当前对许可生热的信号通路的了解棕色/米色脂肪组织非常有限。该应用程序建立在我们的新发现的基础上，即免疫信号许可在棕色的热计划中许可小鼠的脂肪组织。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生热的潜在机制脂肪组织。我们将要解决的三个具体问题是：1）通过什么生理机制棕色脂肪细胞中哪些免疫信号许可证生成？，2）什么是细胞信号传导免疫力调节棕色脂肪细胞中未偶联的呼吸的途径？和3）如何免疫信号调节线粒体蛋白的表达和呼吸？这些目标的成功完成将提供对调节棕色脂肪热发生的细胞和分子途径的新见解，因此促进我们对如何将这种组织靶向人类肥胖症的理解 2型糖尿病。