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How Long-Term Exercise Reshapes the Interorgan Endocrine Landscape
Last reviewed: 09.08.2025
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Scientists from the Molecular Transducers of Physical Activity Consortium (MoTrPAC) have presented the first multisystem study of its kind demonstrating how regular endurance exercise modifies endocrine signaling networks between tissues at the molecular level. The work, led by Cheehoon Ahn and colleagues, is published in the journal Molecular Metabolism.
Why is this important?
Physical activity has long been known as a powerful factor in preventing cardiovascular and metabolic diseases. However, most studies have focused only on changes within skeletal muscle or the heart. The authors went further, asking: which tissues “send” signals (exerkines) and how do they coordinate the benefits of exercise at the level of the whole organism?
Experimental design
- Model and protocol: Male rats received an 8-week course of endurance treadmill training - five times a day, controlled by speed and time. The control group maintained a sedentary lifestyle.
- Multisystem analysis: before and after the intervention, detailed transcriptomic (snRNA-seq) and proteomic (LC-MS/MS) analysis of 16 key tissues was performed: skeletal and cardiac muscles, liver, kidneys, pancreas, different adipose tissue depots (subcutaneous, visceral), as well as lungs, spleen and brain.
- Inferring interorgan connections: QENIE and GD-CAT algorithms made it possible to calculate the strength and direction of endocrine “letters” between tissues based on the level of secreted proteins and their receptors.
Key Discoveries
Subcutaneous adipose tissue is the main “postman”
After training, it was subcutaneous fat that demonstrated the highest number and level of secreted factors directed to other organs. Among them were apotenins, growth factors, and collagen-binding proteins.
Extracellular matrix as a universal mediator
Genes and proteins associated with extracellular matrix synthesis and remodeling (collagens I/III, lamins, fibronectin) were found to be global "messengers" of training effects in all tissues. This points to the importance of connective tissue microstructure in adaptation to loads.
Wnt signaling molecules
Several Wnt family members (Wnt5a, Wnt7b) have been shown to act as molecular bridges between muscle, liver, and adipose tissue, possibly regulating capillary growth and glucose metabolism.
Response Regulatory Organs
In addition to fat and muscle, the liver and heart actively sent “letters” back to the muscles and brain, forming closed feedback loops that enhance energy metabolism and stress resistance.
Practical perspectives
- Search for new biomarkers. Secreted messenger proteins can be studied as indicators of training effectiveness or early signals of fatigue.
- "Non-weight bearing exercise" therapy: Identified exerkines (e.g. specific Wnt ligands) may form the basis of "exercise pills" for sedentary patients.
- Personalization of training programs. The atlas of interorgan connections will help to adapt the intensity and duration of the load to individual tissue reactions.
Conclusion
This study highlights that running and other endurance exercises are not just a muscle pump, but also a powerful endocrine activation of virtually all organs. The exerkine map created by MoTrPAC will pave the way for new diagnostic and therapeutic strategies to help maximize the benefits of exercise.