Molecular Choreography of Acute Exercise

Kévin Contrepois; Si Wu; Kegan J Moneghetti; Daniel Hornburg; Sara Ahadi; Ming-Shian Tsai; Ahmed A Metwally; Eric Wei; Brittany Lee-McMullen; Jeniffer V Quijada; Songjie Chen; Jeffrey W Christle; Mathew Ellenberger; Brunilda Balliu; Shalina Taylor; Matthew G Durrant; David A Knowles; Hani Choudhry; Melanie Ashland; Amir Bahmani; Brooke Enslen; Myriam Amsallem; Yukari Kobayashi; Monika Avina; Dalia Perelman; Sophia Miryam Schüssler-Fiorenza Rose; Wenyu Zhou; Euan A Ashley; Stephen B Montgomery; Hassan Chaib; Francois Haddad; Michael P Snyder

doi:10.1016/j.cell.2020.04.043

Molecular Choreography of Acute Exercise

Cell. 2020 May 28;181(5):1112-1130.e16. doi: 10.1016/j.cell.2020.04.043.

Authors

Kévin Contrepois¹, Si Wu², Kegan J Moneghetti³, Daniel Hornburg², Sara Ahadi², Ming-Shian Tsai², Ahmed A Metwally², Eric Wei², Brittany Lee-McMullen², Jeniffer V Quijada², Songjie Chen², Jeffrey W Christle⁴, Mathew Ellenberger², Brunilda Balliu⁵, Shalina Taylor⁶, Matthew G Durrant², David A Knowles⁷, Hani Choudhry⁸, Melanie Ashland², Amir Bahmani², Brooke Enslen², Myriam Amsallem⁹, Yukari Kobayashi⁹, Monika Avina², Dalia Perelman², Sophia Miryam Schüssler-Fiorenza Rose², Wenyu Zhou², Euan A Ashley¹⁰, Stephen B Montgomery¹¹, Hassan Chaib², Francois Haddad¹², Michael P Snyder¹³

Affiliations

¹ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
² Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
³ Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia; Stanford Sports Cardiology, Department of Medicine, Stanford University, Stanford, CA, USA.
⁴ Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Sports Cardiology, Department of Medicine, Stanford University, Stanford, CA, USA.
⁵ Department of Pathology, Stanford University, Stanford, CA, USA.
⁶ Pediatrics Department, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Department of Radiology, Stanford University, Stanford, CA, USA.
⁸ Department of Biochemistry, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia.
⁹ Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Center for Undiagnosed Diseases, Stanford University, Stanford, CA, USA.
¹¹ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA.
¹² Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA. Electronic address: fhaddad@stanford.edu.
¹³ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA. Electronic address: mpsnyder@stanford.edu.

Abstract

Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.

Keywords: cardiopulmonary exercise testing; fitness; insulin resistance; multi-omics; outlier analysis; peak VO(2); physical activity; predictive analytics; systems biology; time-series analysis.

Publication types

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

MeSH terms

Aged
Biomarkers / metabolism
Energy Metabolism / physiology*
Exercise / physiology*
Female
Humans
Insulin / metabolism
Insulin Resistance
Leukocytes, Mononuclear / metabolism
Longitudinal Studies
Male
Metabolome
Middle Aged
Oxygen / metabolism
Oxygen Consumption
Proteome
Transcriptome

Substances

Biomarkers
Insulin
Proteome
Oxygen

Abstract

Publication types

MeSH terms

Substances

Grants and funding