Atlas of exercise metabolism reveals time-dependent signatures of metabolic homeostasis.

Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. To understand how tissues independently and collectively respond to timed exercise, we applied a systems biology approach. We mapped and compared global metabolite responses of seven different mouse tissues and serum after an acute exercise bout performed at different times of the day. Comparative analyses of intra- and inter-tissue metabolite dynamics, including temporal profiling and blood sampling across liver and hindlimb muscles, uncovered an unbiased view of local and systemic metabolic responses to exercise unique to time of day. This comprehensive atlas of exercise metabolism provides clarity and physiological context regarding the production and distribution of canonical and novel time-dependent exerkine metabolites, such as 2-hydroxybutyrate (2-HB), and reveals insight into the health-promoting benefits of exercise on metabolism. [Display omitted] • Time of exercise defines system-wide activation of energy metabolism • Exercise timing rewires intra-tissue and inter-tissue metabolite correlations • Maintenance of inter-tissue metabostasis is specified by exercise time • Comparative analyses reveal time- and tissue-dependent exerkines Tissue sensitivity and response to exercise vary according to time of day. Sato et al. present an atlas of exercise metabolism, including global metabolomics profiling of multiple tissues, combined with arteriovenous sampling of hindlimb muscle and sampling across the liver to verify net uptake and release of time- and exercise-dependent signaling biochemicals. [ABSTRACT FROM AUTHOR]