Ribosome Heterogeneity as a Mechanism for Metabolic Regulation

核糖体异质性作为代谢调节机制

基本信息

批准号：
10242772
负责人：
JEAN E. SCHAFFER
金额：
$ 81.44万
依托单位：
JOSLIN DIABETES CENTER
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：
2018-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10242772
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

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

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项目摘要

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.

项目摘要/摘要肥胖和代谢综合征的当前流行与饮食和生活方式的改变有关。尽管人体组织对体育活动的响应表现出明显的代谢可塑性，并且饮食暴露，我们对基于有益或有害影响的机制的理解骨骼肌和肝代谢上的运动或营养暴露是不完整的。目标的目标研究是为了发现新的机制，这些机制是增强的骨骼肌胰岛素敏感性的基础急性运动和肝葡萄糖稳态变化和胰岛素敏感性的变化响应和时间限制的喂养范例。我将测试重塑的根本新颖假设这些组织中的核糖体迅速产生蛋白质组的变化，并用作机制代谢可塑性。这项工作将促进我们对环境线索如何塑造代谢的理解生理学，并有可能确定旨在改善人类的预防疗法的新靶标代谢健身。