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 high fat diet 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.