Regulation of glycogen in health and disease

健康和疾病中糖原的调节

基本信息

批准号：
9615724
负责人：
ALAN R. SALTIEL
金额：
$ 48.83万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9615724
关键词：
Acute Adipocytes Adipose tissue Attention Attenuated Brown Fat Cells Chronic Complex Cues Data Deposition Diabetes Mellitus Diet Disease Energy Metabolism Ensure Epidemic Event Expenditure Fasting Fatty Liver Fatty acid glycerol esters Feedback Gene Expression Genes Glucose Glucose-6-Phosphate Glycogen Glycogen (Starch) Synthase Glycogen Phosphorylase Glycogenolysis Inhibition Health Heart Diseases Hepatic Hepatocyte High Fat Diet Homeostasis In Vitro Infiltration Inflammation Inflammatory Insulin Insulin Receptor Knock-out Knockout Mice Link Lipids Lipolysis Liver Liver diseases Metabolic Metabolism Modeling Molecular Mus Muscle Non-Insulin-Dependent Diabetes Mellitus Obesity Overnutrition Pathologic Pathway interactions Patients Phosphoric Monoester Hydrolases Phosphorylases Phosphorylation Phosphotransferases Physiological Play Predisposition Process Protein Dephosphorylation Protein Kinase Protein phosphatase Regulation Role Scaffolding Protein Signal Transduction Specificity TBK1 gene TSC1/2 gene Tissues Uncertainty chemokine energy balance extracellular feeding glycogen metabolism in vivo innovation insight lipid biosynthesis lipid metabolism liver inflammation macrophage mouse model non-alcoholic fatty liver disease overexpression oxidation protein activation response restoration scaffold

项目摘要

There is little doubt that we are in the midst of a worldwide epidemic of obesity, diabetes and fatty liver disease, and disruptions in energy balance are at the heart of these disorders. The first option for energy storage and utilization in metabolically active tissues such as liver, fat and muscle is glycogen. We propose that the regulation of glycogen metabolism is comprised of complex feedback and feedforward pathways, and as such, glycogen itself plays a major role in the overall control of energy disposition in liver and adipose tissue. Glycogen represents the first choice for energy storage and utilization in both tissues, but also serves as a modulator of metabolism in physiological and pathological states, directing the cell to utilize or store energy. We will explore this hypothesis with three aims: 1) We will investigate the molecular mechanisms whereby insulin controls glycogen synthesis; 2) We will evaluate the mechanisms and consequences of increased glycogen accumulation in obesity; and 3) We will evaluate the role of glycogen accumulation in sustaining low grade, chronic inflammation.

毫无疑问，我们正处于肥胖、糖尿病和脂肪肝疾病的全球流行之中，而能量平衡的破坏是这些疾病的核心。肝脏、脂肪和肌肉等代谢活跃组织中能量储存和利用的首选是糖原。我们认为糖原代谢的调节由复杂的反馈和前馈途径组成，因此，糖原本身在肝脏和脂肪组织能量分布的总体控制中发挥着重要作用。糖原是两种组织中能量储存和利用的首选，但也可作为生理和病理状态下新陈代谢的调节剂，指导细胞利用或储存能量。我们将通过三个目标来探索这一假设：1）我们将研究胰岛素控制糖原合成的分子机制； 2）我们将评估肥胖症中糖原积累增加的机制和后果； 3）我们将评估糖原积累在维持低度慢性炎症中的作用。