Abstract
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.
Originalsprog | Engelsk |
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Artikelnummer | e11 |
Tidsskrift | Cell Metabolism |
Vol/bind | 35 |
Udgave nummer | 7 |
Sider (fra-til) | 1261-1279 |
Antal sider | 19 |
ISSN | 1550-4131 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:We thank members of the Long, Bertozzi, and Svensson labs for helpful discussions. We gratefully acknowledge the staff at the Penn Vector Core (RRID: SCR_022432 ) for the production of AAVs. This work was supported by the US National Institutes of Health ( DK105203 and DK124265 to J.Z.L., DK125260 and DK111916 to K.J.S., and K99GM147304 to N.M.R.), the Wu Tsai Human Performance Alliance (research grant to J.Z.L. and postdoctoral fellowship to X.L.), the Stanford Diabetes Research Center ( P30DK116074 ), the Stanford Cardiovascular Institute (CVI), the Weintz Family COVID-19 research fund (K.J.S.), the American Heart Association (AHA), the Stanford School of Medicine , the Jacob Churg Foundation (K.J.S.), the McCormick and Gabilan Award (K.J.S.), the Vanessa Kong-Kerzner Foundation (graduate fellowship to W.W.), the American Heart Association (postdoctoral fellowship to M.Z.), Fundacion Alfonso Martin Escudero (postdoctoral fellowship to M.D.M.-G.), Independent Research Fund Denmark ( 2030-00007A ), and the Lundbeck Foundation ( R380-2021-1451 ) (S.H.R.).
Funding Information:
We thank members of the Long, Bertozzi, and Svensson labs for helpful discussions. We gratefully acknowledge the staff at the Penn Vector Core (RRID: SCR_022432) for the production of AAVs. This work was supported by the US National Institutes of Health (DK105203 and DK124265 to J.Z.L. DK125260 and DK111916 to K.J.S. and K99GM147304 to N.M.R.), the Wu Tsai Human Performance Alliance (research grant to J.Z.L. and postdoctoral fellowship to X.L.), the Stanford Diabetes Research Center (P30DK116074), the Stanford Cardiovascular Institute (CVI), the Weintz Family COVID-19 research fund (K.J.S.), the American Heart Association (AHA), the Stanford School of Medicine, the Jacob Churg Foundation (K.J.S.), the McCormick and Gabilan Award (K.J.S.), the Vanessa Kong-Kerzner Foundation (graduate fellowship to W.W.), the American Heart Association (postdoctoral fellowship to M.Z.), Fundacion Alfonso Martin Escudero (postdoctoral fellowship to M.D.M.-G.), Independent Research Fund Denmark (2030-00007A), and the Lundbeck Foundation (R380-2021-1451) (S.H.R.). Conceptualization, W.W. N.M.R. and J.Z.L.; methodology, W.W. N.M.R. and X.L.; investigation, W.W. N.M.R. X.L. X.S. S.H.R. J.G. M.Z. M.D.M.-G. H.B. A.S.-H.T. V.L.L. W.H. and A.L.W.; writing – original draft, W.W. N.M.R. and J.Z.L.; writing – review & editing, W.W. N.M.R. X.L. and J.Z.L.; resources, J.Z.L. C.R.B. K.J.S. and M.P.S.; supervision and funding acquisition, J.Z.L. and C.R.B. Stanford University has filed a provisional patent on extracellular CES2 proteins and methods of use.
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© 2023 Elsevier Inc.