Atlas of Exercise Metabolism Reveals Time-Dependent Signatures of Metabolic Homeostasis

Exercise provides a myriad of health benefits, with mode, intensity, duration, and frequency all determining magnitude of effect. Tissue sensitivity and response to exercise varies according to time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. Here, we mapped and integrated the global metabolite response of 8 different mouse tissues after acute exercise at different times of day. Applying a systems biology approach, we revealed how tissues independently and collectively respond to exercise. Comparative analysis underscored how tissues are metabolically connected and revealed how metabolites are used for communication among tissues to maintain metabolic homeostasis in response to exercise. Specific metabolic outcomes were determined by time of exercise. This comprehensive atlas of exercise responses provides clarity and context regarding the production and distribution of signaling metabolites and reveals insight into the health promoting benefits on metabolism.