Regulation of Glycogen in Health and Disease

糖原在健康和疾病中的调节

• 批准号: 9925085
• 负责人: ALAN R. SALTIEL
• 金额: $ 48.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 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/9925085
• 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; Obesity Epidemic; 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; conditional knockout; 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

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、糖尿病和脂肪肝的全球流行之中，而能量平衡的破坏是这些疾病的核心。在肝脏、脂肪和肌肉等代谢活跃的组织中，能量储存和利用的第一选择是糖原。我们认为糖原代谢的调节是由复杂的反馈和前馈途径组成的，因此，糖原本身在肝脏和脂肪组织能量配置的整体控制中起着重要作用。糖原是两种组织能量储存和利用的首选，同时也是生理和病理状态下的代谢调节剂，指导细胞利用或储存能量。我们将从三个方面探讨这一假设：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级别慢性炎症中的作用。