Researchers Discover ‘Switch’ for Desire to Exercise

Exercising is good for your health, but it’s not always appealing. A study led by Guadalupe Sabio of the National Cancer Research Center (CNIO) may have discovered a “switch” that activates the desire to move, as it shows that during exercise, the muscle activates proteins that encourage additional activity. The study is published in Scientific progress.

“We have discovered how the muscle itself regulates interest in exercise through a signalling pathway between the muscle and the brain that we did not know and which is one of those responsible – as there must be several – for the fact that, when we exercise, we feel the impulse to train even more,” explains Sabio, head of the Interaction between organs in metabolic diseases group at the CNIO.

The article also shows that proteins produced by muscles during exercise regulate each other, preventing the desire to exercise from harming the body.

The results are based on data obtained from animal models and humans (volunteers who performed controlled exercises and obese patients). This suggests that the identified signaling pathway “plays a crucial role in the regulation of physical activity in mice and humans” and “highlights the potential therapeutic importance of this pathway in the treatment of obesity and metabolic diseases,” the authors write.

The first co-authors of the study are Leticia Herrera and Cintia Folgueira, researchers from the National Cardiovascular Research Center (CNIC).

Three proteins that influence the desire for physical activity

The group observed that when muscles contract repeatedly and intensely, due to exercise, the pathways of two proteins of the same family are activated: p38α and p38γ. The interest in physical activity is more or less great depending on the degree of activation of each of these two proteins, reveals the study.

A third protein is also involved: interleukin 15 (IL-15). The authors observed that activation of p38γ by exercise induces the production of IL-15, and that this protein has a direct effect on the part of the cerebral cortex that controls movement, the motor cortex.

The increase in IL-15 in the blood works as a signal to the brain to improve motor activity, prompting animals to voluntarily become more active.

“In this study, we revealed that exercise-induced activation of muscle p38γ protein leads to IL-15 production, which then enhances spontaneous physical activity. Furthermore, we observed the presence of this p38γ/IL-15 axis in humans after exercise, highlighting the clinical relevance of this signaling pathway in promoting exercise behavior in the population,” the authors state.

The effect of regular training

When the animals were subjected to regular exercise, p38γ activation was also higher than p38α activation. This leads the research team to postulate that the training itself maintains the desire to exercise.

In animals fed a high-fat diet and obese, regular exercise was found to be beneficial: it improved metabolism and reduced the tendency to diabetes and fat accumulation, particularly in the liver.

In humans

In humans, both p38 proteins have been observed to be activated in muscles subjected to increasing intensity exercise. Blood levels of IL-15 have also been observed to increase, with obese patients having lower values.

This link with obesity is essential, say the authors, this disease being the most common metabolic disorder in the world. Regular exercise is considered an effective strategy for the prevention and treatment of obesity.

“The correlation between p38γ activation in human muscle during acute exercise and increased blood IL-15 levels underscores the potential therapeutic importance of this pathway in the treatment of obesity and metabolic diseases,” the authors write in their paper.

A biomarker of the desire to exercise

For Sabio, one of the next steps will be to confirm that IL-15 is indeed a blood marker of exercise desire. Once this is proven, “we can study whether different types of exercise (weights, running, CrossFit, etc.) stimulate this axis differently, and also whether it has the same effect on obese and non-obese people. This can help coaches and personal trainers design their programs more effectively.”

She adds that “we could even consider creating an IL-15 drug for people who need the positive effects of exercise more and are less likely to do it or maintain it. For example, people who are obese.”

Guadalupe Sabio already plans to use this model to try to better determine the relationship between exercise, longevity and cancer and to discover the mechanisms that regulate it.