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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 中碱下丘脑（MBH）在控制肝葡萄糖稳态中起关键作用。 MBH感受到循环营养素，例如葡萄糖和脂肪酸以及瘦素和胰岛素等激素，从而评估了生物体的能量状态。当餐后循环水平在餐后状态下升高时，从MBH降下来的途径被激活并抑制肝葡萄糖（HGP）。 在胰岛素（IR）状态胰岛素中，胰岛素无法抑制肝葡萄糖产生（HGP），这部分是由于HGP的MBH控制丧失所解释的。通过这些中心途径的激活在周围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来自资源的高灵敏度，高分辨率LC-MS定量蛋白质组学，以确定由MBH激活诱导的总组织中的蛋白质水平以及总细胞隔室（包括细胞体，线粒体和膜级分）的差异。我们旨在通过应用晚期蛋白质组学技术来确定几种亚细胞提取物中蛋白质丰度以及丝氨酸/苏氨酸磷酸化差异的差异。 我们的目标是鉴定肝组织中的关键分子途径，以控制脂质和葡萄糖代谢。 这些研究有可能促进发现新的治疗靶标，从而降低胰岛素抵抗并避免或改善2型糖尿病。蛋白质组学数据将为NIH R01应用程序以及未来出版物提供初步数据。