Ribosome Heterogeneity as a Mechanism for Metabolic Regulation

核糖体异质性作为代谢调节机制

• 批准号: 10469691
• 负责人: JEAN E. SCHAFFER
• 金额: $ 79.77万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469691
• 关键词: Acute; Cues; Diabetes Mellitus; Diet; Exercise; Goals; Hepatic; Heterogeneity; Human; Life Style; Link; Metabolic; Metabolic syndrome; Metabolism; Nutrient; Obesity Epidemic; Physical activity; Physiology; Preventive therapy; Proteome; Reaction Time; Regulation; Ribosomes; Shapes; Skeletal Muscle; Testing; Time-restricted feeding; Tissues; Work; blood glucose regulation; dietary; human tissue; improved; insulin sensitivity; liver metabolism; metabolic fitness; novel; response; skeletal muscle metabolism

PROJECT SUMMARY/ABSTRACT The current epidemic of obesity and metabolic syndrome has been linked to alterations in diet and lifestyle. Although human tissues demonstrate remarkable metabolic plasticity in response to physical activity and dietary exposures, our understanding of the mechanisms that underlie the beneficial or deleterious effects of exercise or nutrient exposures on skeletal muscle and hepatic metabolism are incomplete. The goal of this study is to uncover new mechanisms that underlie enhanced skeletal muscle insulin sensitivity following an acute bout of exercise and changes in hepatic glucose homeostasis and insulin sensitivity in refeeding responses and time-restricted feeding paradigms. I will test the radically novel hypothesis that remodeling of ribosomes in these tissues rapidly generates changes in the proteome and serves as a mechanism for metabolic plasticity. This work will advance our understanding of how environmental cues shape metabolic physiology and has the potential to identify new targets for preventive therapies aimed at improving human metabolic fitness.

项目概要/摘要 当前肥胖和代谢综合征的流行与饮食和生活方式的改变有关。 尽管人体组织表现出显着的代谢可塑性以响应身体活动和 饮食暴露，我们对潜在有益或有害影响的机制的理解 运动或营养暴露对骨骼肌和肝脏代谢不完全。此举的目标 研究的目的是揭示骨骼肌胰岛素敏感性增强的新机制 急性运动以及重新喂养时肝葡萄糖稳态和胰岛素敏感性的变化 反应和限时喂养范例。我将测试一个全新的假设，即重塑 这些组织中的核糖体迅速产生蛋白质组变化，并作为一种机制 代谢可塑性。这项工作将增进我们对环境因素如何影响代谢的理解 生理学，并有可能确定旨在改善人类健康的预防性治疗的新目标 代谢健康。