Ribosome Heterogeneity as a Mechanism for Metabolic Regulation

项目总结/摘要 目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。 尽管人体组织在响应体力活动和运动时表现出显著的代谢可塑性， 饮食暴露，我们对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的影响是不完全的。这个目标 这项研究旨在揭示骨骼肌胰岛素敏感性增强的新机制， 急性运动与再喂养时肝脏葡萄糖稳态和胰岛素敏感性的变化 反应和时间限制的喂养模式。我将测试一个全新的假设， 这些组织中的核糖体迅速引起蛋白质组的变化，并作为一种机制， 代谢可塑性这项工作将促进我们对环境因素如何塑造代谢的理解 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靶点。 代谢健康

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.