PGC-1beta in the Regulation of Hepatic Lipid Metabolism

PGC-1beta 对肝脏脂质代谢的调节

基本信息

批准号：
7315528
负责人：
Jiandie D Lin
金额：
$ 27.86万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7315528
关键词：
Apolipoproteins Biochemical Biological Blood Glucose Cholesterol Chromatin Remodeling Factor Condition Data Disease Dyslipidemias Epidemic Fatty Acids Fatty acid glycerol esters Gap Junctions Gene Expression Genome Goals Hepatic Homeostasis Hormonal Hyperglycemia Hyperlipidemia Hypertriglyceridemia Insulin Resistance Link Lipids Lipoproteins Liver Maintenance Mediating Metabolic Metabolic Diseases Metabolic syndrome Metabolism Molecular Mus Nexus (resin cement)Non-Insulin-Dependent Diabetes Mellitus Nuclear Hormone Receptors Nutritional Obesity Pathogenesis Pathway interactions Plasma Play Positioning Attribute RNA Interference Recruitment Activity Regulation Research Personnel Role Signal Pathway Signal Transduction Syndrome Testing Transcription Coactivator Transgenic Mice Transgenic Organisms Triglycerides adenoviral-mediated base blood glucose regulation cardiovascular disorder risk chromatin remodeling insight insulin sensitivity lipid biosynthesis lipid metabolism lipid transport lipoprotein triglyceride novel programs saturated fat transcription factor

项目摘要

DESCRIPTION (provided by applicant): Metabolic syndrome is emerging as a global epidemic. The profound metabolic dysregulation in this syndrome is typically manifested by clustering of several disorders, including obesity, type 2 diabetes, and dyslipidemia, and is associated with an increased risk for cardiovascular disease. Hepatic lipogenesis and lipoprotein metabolism are important in maintaining lipid homeostasis. There is increasing evidence that hepatic lipid metabolism plays an important role in the pathogenesis of key aspects of metabolic syndrome, including hyperlipidemia, hyperglycemia, and insulin resistance. We have recently demonstrated that transcriptional coactivator PGC-1? coordinately regulates lipogenesis, lipid trafficking, and lipoprotein metabolism in the liver. These data suggest that PGC-1? is a central component of the regulatory network in maintaining lipid homeostasis. The major goals of this proposal are to test the hypothesis that PGC-1? is involved in the pathogenesis of metabolic syndrome and serves as a molecular link between lipid metabolism and insulin resistance. In addition, molecular components of the PGC-1? pathway will be dissected and analyzed. Aim 1 is to determine evaluate the role of PGC-1? in the pathogenesis of metabolic dysregulation and in linking lipid metabolism to insulin resistance. Aim 2 is to define transcriptional components underlying PGC-1? regulation of triglyceride and lipoprotein metabolism. Aim 3 is to investigate the role of chromatin remodeling in lipid metabolism. Completion of this proposal will define the molecular details of a major regulatory network in the maintenance of lipid homeostasis.

描述（由申请人提供）：代谢综合征正在成为一种全球流行病。该综合征中严重的代谢失调通常表现为多种疾病的聚集，包括肥胖、2 型糖尿病和血脂异常，并且与心血管疾病风险增加相关。肝脏脂肪生成和脂蛋白代谢对于维持脂质稳态很重要。越来越多的证据表明，肝脏脂质代谢在代谢综合征关键方面的发病机制中发挥着重要作用，包括高脂血症、高血糖和胰岛素抵抗。我们最近证明了转录共激活因子 PGC-1？协调调节肝脏中的脂肪生成、脂质运输和脂蛋白代谢。这些数据表明PGC-1？是维持脂质稳态调节网络的核心组成部分。该提案的主要目标是检验 PGC-1？参与代谢综合征的发病机制，并作为脂质代谢和胰岛素抵抗之间的分子联系。另外，PGC-1的分子成分？路径将被剖析和分析。目的1是确定评估PGC-1的作用？代谢失调的发病机制以及脂质代谢与胰岛素抵抗的联系。目标 2 是定义 PGC-1 背后的转录成分？调节甘油三酯和脂蛋白代谢。目标 3 是研究染色质重塑在脂质代谢中的作用。该提案的完成将定义维持脂质稳态的主要调控网络的分子细节。