Systems Biology of Insulin Resistance

胰岛素抵抗的系统生物学

• 批准号: 8053081
• 负责人: Roger J Davis
• 金额: $ 218.04万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8053081
• 关键词: Achievement; American; Biochemical; Cells; Computer Simulation; Data; Data Analyses; Development; Diet; Disease; Fatty acid glycerol esters; Functional disorder; Gene Expression; Genomics; Goals; Health; Hepatic; Human; Hyperglycemia; Insulin Resistance; Knowledge; Laboratories; Lead; Liver; Mass Spectrum Analysis; Mediating; Metabolic syndrome; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Physiological; Physiology; Principal Investigator; Procedures; Research; Research Proposals; Signal Pathway; Signal Transduction; Signal Transduction Pathway; System; Systems Biology; Testing; Therapeutic Intervention; Transcription factor genes; base; design; feeding; novel therapeutics; programs; protein expression; response; treatment strategy

DESCRIPTION (provided by applicant): Human obesity represents a serious world-wide health problem. One consequence of obesity is the development of insulin resistance, hyperglycemia, and metabolic syndrome that can lead to cell dysfunction and type 2 diabetes. It is therefore important that we gain an understanding of the physiology and pathophysiology of the development of obesity because this knowledge represents a basis for the design of potential therapeutic interventions. A significant challenge to understanding diet-induced obesity is the complexity of the signal transduction pathways that mediate the response. Indeed, these signaling pathways function within an interacting network. Here we propose to employ a systems biology approach to understanding the response to feeding a high fat diet by combining physiological analysis together with quantitative analysis of the signal transduction networks and the genomic response. This analysis requires the coordinated collaborative efforts of several laboratories with complementary expertise together with robust data analysis and computational modeling. We will focus our analysis on the liver. The overall goal of this research program is to understand the mechanism of the hepatic response to diet-induced obesity. Achievement of the goals of this proposal will increase understanding of the molecular response to obesity. We anticipate that the successful completion of this research program will lead to the identification of nodes in the signaling network that may represent a basis for the design of novel therapeutic strategies for the treatment of metabolic syndrome and type II diabetes. The Specific Aims of this proposal are to: 1. Examine the hepatic response to feeding a high fat diet. 2. Integrate data analysis using computational modeling. 3. Test predictions obtained from computational modeling. PUBLIC HEALTH RELEVANCE: Metabolic syndrome and type II diabetes are serious diseases that have a profound impact on the health of many Americans; it is essential that we develop new treatment options for these diseases. The purpose of this research proposal is to perform a systems biology analysis of the hepatic response to diet-induced obesity. We anticipate that this information will provide a basis for the design of novel therapeutic strategies for the treatment of metabolic syndrome and type II diabetes.

描述（由申请人提供）：人类肥胖代表了一个严重的全球健康问题。肥胖的结果之一是胰岛素抵抗，高血糖和代谢综合征的发展可能导致细胞功能障碍和2型糖尿病。因此，重要的是我们了解肥胖发展的生理学和病理生理学，因为这种知识代表了设计潜在治疗干预措施的基础。 理解饮食引起的肥胖症的重大挑战是介导反应的信号转导途径的复杂性。实际上，这些信号通路在交互网络中起作用。在这里，我们建议采用系统生物学方法来理解对高脂饮食的反应，通过将生理分析与信号转导网络的定量分析和基因组反应结合在一起。该分析要求几个实验室与互补专业知识以及强大的数据分析和计算建模的协作协作努力。 我们将把分析重点放在肝脏上。该研究计划的总体目标是了解肝脏对饮食引起的肥胖症的反应机制。实现该提案的目标将增加对分子对肥胖反应的理解。我们预计，该研究计划的成功完成将导致信号网络中的节点鉴定，这可能代表了设计新型治疗策略的基础，以治疗代谢综合征和II型糖尿病。该提案的具体目的是：1。检查肝脏对喂养高脂肪饮食的反应。 2。使用计算建模整合数据分析。 3。从计算建模获得的测试预测。 公共卫生相关性：代谢综合征和II型糖尿病是严重疾病，对许多美国人的健康产生了深远的影响；我们必须为这些疾病开发新的治疗选择。 这项研究建议的目的是对肝脏对饮食引起的肥胖症的肝反应进行系统生物学分析。我们预计，此信息将为设计新型治疗策略的设计提供代谢综合征和II型糖尿病的基础。