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. [Display omitted] •An organism-wide cell-type-specific secretome atlas after exercise training in mice•Exercise training induces cell-type-specific and bidirectional secretome changes•Pdgfra+ cells are highly responsive to exercise training•Secreted CES2 proteins improve metabolic health and enhance running endurance Wei et al. use proteomics to identify cellular secretome changes in response to exercise training at an organism-wide scale. Using this dataset, Wei et al. identified two exercise-inducible secreted proteins from the liver that enhance running performance and improve metabolic health.