Remodeling p38 signaling in muscle controls locomotor activity via IL-15

Skeletal muscle has gained recognition as an endocrine organ releasing myokines upon contraction during physical exercise. These myokines exert both local and pleiotropic health benefits, underscoring the crucial role of muscle function in countering obesity and contributing to the overall positive...

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Published in:Science advances 2024-08, Vol.10 (33), p.eadn5993
Main Authors: Folgueira, Cintia, Herrera-Melle, Leticia, López, Juan Antonio, Galvan-Alvarez, Victor, Martin-Rincon, Marcos, Cuartero, María Isabel, García-Culebras, Alicia, Dumesic, Phillip A, Rodríguez, Elena, Leiva-Vega, Luis, León, Marta, Porteiro, Begoña, Iglesias, Cristina, Torres, Jorge L, Hernández-Cosido, Lourdes, Bonacasa, Clara, Marcos, Miguel, Moro, María Ángeles, Vázquez, Jesús, Calbet, Jose A L, Spiegelman, Bruce M, Mora, Alfonso, Sabio, Guadalupe
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedicine and Life Sciences
Exercise - physiology
Humans
Interleukin-15 - metabolism
Locomotion
Male
MAP Kinase Signaling System
Mice
Muscle, Skeletal - metabolism
Obesity - metabolism
p38 Mitogen-Activated Protein Kinases - metabolism
Physiology
SciAdv r-articles
Signal Transduction
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Summary:Skeletal muscle has gained recognition as an endocrine organ releasing myokines upon contraction during physical exercise. These myokines exert both local and pleiotropic health benefits, underscoring the crucial role of muscle function in countering obesity and contributing to the overall positive effects of exercise on health. Here, we found that exercise activates muscle p38γ, increasing locomotor activity through the secretion of interleukin-15 (IL-15). IL-15 signals in the motor cortex, stimulating locomotor activity. This activation of muscle p38γ, leading to an increase locomotor activity, plays a crucial role in reducing the risk of diabetes and liver steatosis, unveiling a vital muscle-brain communication pathway with profound clinical implications. The correlation between p38γ activation in human muscle during acute exercise and increased blood IL-15 levels highlights the potential therapeutic relevance of this pathway in treating obesity and metabolic diseases. These findings provide valuable insights into the molecular basis of exercise-induced myokine responses promoting physical activity.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.adn5993