The study by Folgueira et al. (2024) published in Science Advances brings a discovery that could revolutionize the way we understand the relationship between physical exercise, metabolic health and motivation for physical activity. The research identified a crucial communication pathway between the muscle and the brain, mediated by the p38γ protein and the cytokine IL-15, which drives spontaneous locomotor activity and protects against obesity, diabetes and hepatic steatosis.
The discovery that p38γ, activated in muscle during exercise, stimulates the production of IL-15, which in turn signals the cerebral motor cortex to increase voluntary physical activity, opens up a range of possibilities for the development of new therapies to combat obesity and related metabolic diseases. The finding that individuals with obesity have reduced levels of IL-15 in their blood reinforces the clinical importance of this signaling pathway.
This research sheds light on the molecular mechanisms by which exercise promotes physical activity, suggesting that p38γ and IL-15 act as a reward system, encouraging regular exercise. Additionally, the study reveals an intriguing mechanism of physical activity control, where p38α acts as a brake, inhibiting p38γ and IL-15 production, possibly to prevent overexercise and exhaustion.
In summary, the work of Folgueira et al. (2024) represents a significant advance in the understanding of the complex interaction between muscle and brain, paving the way for the development of innovative therapeutic strategies to combat obesity and promote metabolic health through the stimulation of physical activity. The discovery of the p38γ/IL-15 pathway invites us to rethink the way we view exercise, not only as a tool for weight loss, but also as a powerful ally in promoting mental health and general well-being.
Reference:
Folgueira, C., Herrera-Melle, L., López, JA, Galvan-Alvarez, V., Martin-Rincon, M., Cuartero, MI, … & Sabio, G. (2024). Remodeling p38 signaling in muscle controls locomotor activity via IL-15. Science Advances, 10(33), eadn5993.
