PGC-1beta in the Regulation of Hepatic Lipid Metabolism

PGC-1beta 对肝脏脂质代谢的调节

• 批准号: 8010020
• 负责人: Jiandie D Lin
• 金额: $ 3.2万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8010020
• 关键词: Apolipoproteins; Biochemical; Biological; Blood Glucose; Cholesterol; Chromatin Remodeling Factor; Data; Disease; Dyslipidemias; Epidemic; Fatty Acids; Fatty acid glycerol esters; Gap Junctions; Gene Expression; Goals; Hepatic; Homeostasis; Hormonal; Hyperglycemia; Hyperlipidemia; Hypertriglyceridemia; Insulin Resistance; Link; Lipids; Lipoproteins; Liver; Maintenance; Mediating; Metabolic; Metabolic Diseases; Metabolic syndrome; Metabolism; Molecular; Mus; 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; genome-wide; insight; insulin sensitivity; lipid biosynthesis; lipid metabolism; lipid transport; lipoprotein triglyceride; novel; programs; saturated fat; transcription factor

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全球流行病。该综合征的深刻代谢失调通常由多种疾病的聚类（包括肥胖，2型糖尿病和血脂异常）表现出来，并且与心血管疾病的风险增加有关。肝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，肝脂质代谢在代谢综合征的关键方面的发病机理中起着重要作用，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吗？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？是维持脂质稳态的监管网络的核心组成部分。该提案的主要目标是检验PGC-1的假设？参与了代谢综合征的发病机理，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？途径将被解剖和分析。 AIM 1是确定评估PGC-1的作用？在代谢失调的发病机理以及将脂质代谢与胰岛素抵抗联系起来的过程中。 AIM 2是定义PGC-1基础的转录组件？调节甘油三酸酯和脂蛋白代谢。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脂质稳态维持主要调节网络的分子细节。