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

Wei Wei; Nicholas M Riley; Xuchao Lyu; Xiaotao Shen; Jing Guo; Steffen H Raun; Meng Zhao; Maria Dolores Moya-Garzon; Himanish Basu; Alan Sheng-Hwa Tung; Veronica L Li; Wentao Huang; Amanda L Wiggenhorn; Katrin J Svensson; Michael P Snyder; Carolyn R Bertozzi; Jonathan Z Long

doi:10.1016/j.cmet.2023.04.011

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

Cell Metab. 2023 Jul 11;35(7):1261-1279.e11. doi: 10.1016/j.cmet.2023.04.011. Epub 2023 May 3.

Authors

Wei Wei¹, Nicholas M Riley², Xuchao Lyu³, Xiaotao Shen⁴, Jing Guo⁵, Steffen H Raun⁶, Meng Zhao⁷, Maria Dolores Moya-Garzon⁸, Himanish Basu⁹, Alan Sheng-Hwa Tung⁸, Veronica L Li¹⁰, Wentao Huang¹¹, Amanda L Wiggenhorn¹⁰, Katrin J Svensson⁷, Michael P Snyder¹², Carolyn R Bertozzi², Jonathan Z Long¹³

Affiliations

¹ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA.
² Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Chemistry, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
³ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Genetics, Stanford University School of Medicine, Stanford, CA 94035, USA.
⁵ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁶ Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁸ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA.
⁹ Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
¹¹ Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
¹² Department of Genetics, Stanford University School of Medicine, Stanford, CA 94035, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
¹³ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA 94305, USA. Electronic address: [email protected].

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.

Keywords: CES2; cell type; energy metabolism; exercise; exercise performance; hepatokine; obesity; secretome; tissue crosstalk.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus*
Mice
Obesity
Proteins
Proteomics
Secretome*

Substances

Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding