RT Journal Article SR Electronic T1 Organism-wide secretome mapping uncovers pathways of tissue crosstalk in exercise JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.11.21.517385 DO 10.1101/2022.11.21.517385 A1 Wei Wei A1 Nicholas M. Riley A1 Xuchao Lyu A1 Xiaotao Shen A1 Jing Guo A1 Meng Zhao A1 Maria Dolores Moya-Garzon A1 Himanish Basu A1 Alan Tung A1 Veronica L. Li A1 Wentao Huang A1 Katrin J. Svensson A1 Michael P. Snyder A1 Carolyn R. Bertozzi A1 Jonathan Z. Long YR 2022 UL http://biorxiv.org/content/early/2022/11/23/2022.11.21.517385.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.