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Organism-wide secretome mapping uncovers pathways of tissue crosstalk in exercise

Wei, W.; Riley, N. M.; Lyu, X.; Shen, X.; Guo, J.; Zhao, M.; Moya-Garzon, M. D.; Basu, H.; Tung, A.; Li, V. L.; Huang, W.; Svensson, K. J.; Snyder, M. P.; Bertozzi, C. R.; Long, J. Z.

2022-11-23 systems biology
10.1101/2022.11.21.517385 bioRxiv
Show abstract

There has been growing interest in identifying blood-borne factors that mediate tissue crosstalk and function as molecular effectors of physical activity. Although past studies have focused on an individual molecule or cell type, the organism-wide secretome response to physical activity has not been evaluated. Here, we use a cell type-specific proteomic approach to generate a 21-cell type, 10-tissue map of exercise-regulated secretomes in mice. Our dataset identifies >200 exercise-regulated cell type-secreted protein pairs, the majority of which have not been previously reported. Pdgfra-cre-labeled secretomes were the most responsive to exercise training. Elevated lactate levels can directly regulate protein secretion. Lastly, we establish an anti-obesity and anti-diabetic role for a proteoform of an intracellular carboxylesterase whose secretion from the liver is induced by exercise training. Together, our data uncover the dynamic remodeling of cell and tissue crosstalk by physical activity.

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