Exercise intensity modulates the human plasma secretome and interorgan communication

Area of Science:

• Exercise physiology
• Metabolomics
• Proteomics
• Cardiometabolic health

Background:

• Exercise is crucial for managing cardiometabolic diseases like obesity, type 2 diabetes, and hypertension.
• The specific circulatory factors mediating exercise benefits and how exercise intensity affects them are not fully understood.
• Understanding interorgan crosstalk regulation by exercise intensity is key to optimizing therapeutic strategies.

Purpose of the Study:

• To investigate the intensity-dependent regulation of interorgan crosstalk by different exercise modes.
• To characterize how sprint-interval exercise (SIE) and moderate-intensity exercise (MIE) differentially affect the plasma proteome and metabolome.
• To map exercise-regulated proteins to their tissue of origin and destination.

Main Methods:

• Conducted a multi-cohort human exercise intervention with SIE and MIE.
• Analyzed plasma proteome and metabolome changes.
• Integrated multi-organ gene and protein expression datasets with in vitro and in vivo tissue sampling.
• Utilized transcriptomic analysis of adipocytes.

Main Results:

• Exercise intensity distinctly modulated the plasma proteome and metabolome in both untrained and trained individuals.
• SIE induced immediate and robust proteomic changes, while MIE showed delayed secretory kinetics.
• Adipocytes exhibited significant transcriptomic remodeling in response to SIE plasma compared to MIE plasma, indicating intensity-dependent sensitivity.

Conclusions:

• Acute exercise elicits an integrated whole-body response.
• Exercise intensity is a critical determinant of interorgan communication.
• Findings provide novel insights into the molecular mechanisms underlying exercise's cardiometabolic benefits.