Organism-wide, cell-type-specific secretome mapping of exercise training in mice

There is a significant 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 training-regulated secretomes in mice. Our dataset identifies >200 exercise training-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. Finally, we show anti-obesity, anti-diabetic, and exercise performance -enhancing activities for proteoforms of intracellular carboxylesterases whose secretion from the liver is induced by exercise training.

Automated summary

There is a need to identify blood-borne factors that mediate tissue crosstalk during physical activity. This study used a cell-type-specific proteomic approach to map exercise training-regulated secretomes in mice, identifying over 200 previously unreported cell-type-secreted protein pairs. The study also found exercise-induced secretion of proteoforms of intracellular carboxylesterases from the liver, which had anti-obesity, anti-diabetic, and exercise performance-enhancing activities.