PROTEOMIC STUDY OF HEPATIC METABOLISM REGULATED BY HYPOTHALAMIC PATHWAYS

下丘脑通路调控的肝脏代谢的蛋白质组学研究

• 批准号: 8365471
• 负责人: CHRISTOPH BUETTNER
• 金额: $ 2.87万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365471
• 关键词: Biology; Data; Event; Fatty Acids; Funding; Future; Glucose; Goals; Grant; Hepatic; Hormones; Hypothalamic structure; Insulin; Insulin Resistance; Leptin; Liver; Membrane; Metabolism; Mitochondria; Molecular; National Center for Research Resources; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Organism; Pathway interactions; Peripheral; Play; Principal Investigator; Proteins; Proteomics; Publications; Research; Research Infrastructure; Resolution; Resources; Role; Serine/Threonine Phosphorylation; Source; Technology; Tissues; United States National Institutes of Health; blood glucose regulation; cost; glucose metabolism; glucose production; lipid metabolism; new therapeutic target

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The medio-basal hypothalamus (MBH) plays a pivotal role in the control of hepatic glucose homeostasis. The MBH senses circulating nutrients like glucose and fatty acids as well as hormones like leptin and insulin and thus assesses the energy state of the organism. When circulating levels of nutrients and insulin are rising during the postprandial state, pathways descending from the MBH are activated and hepatic glucose production (hGP) is suppressed. In the insulin resistant (IR) state insulin fails to suppress hepatic glucose production (hGP) which is partly explained by a loss of the MBH control of hGP. The molecular events that take place in peripheral tissues by the activation of these central pathways are poorly understood. The overall goal of this proposal is to utilize high sensitivity, high resolution LC-MS quantitative proteomics from the resource to identify differences in protein levels in total tissue as well as subcellular compartments (including cytosolic, mitochondria and membrane fractions) that are induced by the activation of the MBH. We aim to identify differences in protein abundances as well as serine/threonine phosphorylation differences in several subcellular extracts by applying the advanced proteomics technologies. Our goal is to identify key molecular pathways in liver tissue that exert control of lipid and glucose metabolism. These studies have the potential to facilitate the discovery of new therapeutic targets that decrease insulin resistance and avert or ameliorate type 2 diabetes. The proteomic data will serve the preliminary data for NIH R01 application as well as for future publications.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 下丘脑中基底层（MBH）在控制肝脏葡萄糖稳态中发挥着关键作用。 MBH 感知循环的营养物质（如葡萄糖和脂肪酸）以及激素（如瘦素和胰岛素），从而评估生物体的能量状态。当餐后状态下营养物质和胰岛素的循环水平上升时，MBH 下行通路被激活，肝葡萄糖生成 (hGP) 受到抑制。 在胰岛素抵抗 (IR) 状态下，胰岛素无法抑制肝葡萄糖生成 (hGP)，部分原因是 MBH 对 hGP 控制的丧失。人们对这些中枢通路激活而在外周组织中发生的分子事件知之甚少。该提案的总体目标是利用资源中的高灵敏度、高分辨率 LC-MS 定量蛋白质组学来识别总组织以及亚细胞区室（包括胞质、线粒体和膜部分）中蛋白质水平的差异，这些差异是由MBH 的激活。我们的目标是通过应用先进的蛋白质组学技术来识别几种亚细胞提取物中蛋白质丰度的差异以及丝氨酸/苏氨酸磷酸化的差异。 我们的目标是确定肝组织中控制脂质和葡萄糖代谢的关键分子途径。 这些研究有可能促进发现新的治疗靶点，从而降低胰岛素抵抗并避免或改善 2 型糖尿病。蛋白质组数据将为NIH R01申请以及未来出版物提供初步数据。