María Carmen Gómez Cabrera
Professor in the Department of Physiology at the University of Valencia
The article is of excellent quality. The authors employ a very elegant and rigorous methodology and experimental design to demonstrate, for the first time, that repeated exercise, what we understand as training, induces lasting increases in the post-exercise activation of a very specific neuronal group: SF1 neurons located in the ventromedial hypothalamus.
While previous studies had shown that acute exercise can transiently activate SF1 neurons in the hypothalamus, this work goes a step further by demonstrating that training produces stable changes in their excitability. These findings indicate that accumulated exercise experience is stored centrally through hypothalamic plasticity mechanisms, representing a substantial advance over previous evidence regarding the function of these neurons.
Overall, the study provides solid evidence that the brain not only responds immediately to exercise but also integrates its prior history, providing a central basis for the metabolic and physiological adaptations induced by training.
The study fits coherently with previous evidence, which had already shown that acute exercise can transiently activate certain neuronal populations in the hypothalamus, including SF1 neurons in the ventromedial hypothalamus. However, until now, it had not been demonstrated that training could induce lasting changes in the activity and functional properties of these neurons, beyond acute responses.
This work demonstrates that training leads to a stable central adaptation. Thus, the study provides a mechanistic basis for understanding how the brain can integrate accumulated exercise experience, complementing the peripheral mechanisms traditionally described in muscle and other tissues.
The implications of these findings are broad. First, they suggest that the central nervous system plays an active role in consolidating training-induced adaptations, which could help explain the interindividual variability in the response to exercise. Furthermore, this conceptual framework helps to understand the lasting effects of exercise on metabolism and health, as well as its protective role against metabolic and neurodegenerative diseases. Finally, it opens new avenues for optimizing exercise-based interventions, considering not only the physical load but also the central mechanisms that determine their effectiveness.
The study has some limitations that should be taken into account. First, most of the experiments were performed in animal models, which raises the need to confirm the extent to which these central mechanisms are extrapolated to humans. Although the hypothalamic pathways involved are well conserved evolutionarily, the clinical translation of these findings will require further studies.
Likewise, although the work convincingly demonstrates that SF1 neuron activity contributes to training-induced adaptations, it does not exclude the essential participation of well-established peripheral mechanisms, such as muscular, cardiovascular, or metabolic adaptations. Exercise is an integrated, multi-organ stimulus, so central mechanisms should be interpreted as modulators or facilitators, rather than as the sole determinants of physical improvement.
Regarding the possibility that brain mechanisms enable or limit physical improvement, the hypothesis is biologically sound. The central nervous system regulates the autonomic response, the use of energy substrates, thermoregulation, perceived exertion, and motivation—all key factors for performance and adaptation to exercise. Therefore, differences in the plasticity or adaptive capacity of these central circuits could significantly contribute to interindividual variability in training response.
Finally, it will be important to determine more precisely how these central mechanisms interact with peripheral signals, and whether there are critical periods, dependent on age, health status, or training context, in which the brain's contribution is particularly relevant.