The benefits of physical exercise may depend on certain brain changes, according to a study in mice

This is a high-quality study that offers a novel idea: that the brain not only responds to exercise, but that it is necessary to consolidate the benefits of repeated training. It introduces the concept that exercise history can be 'recorded' in specific brain circuits.

We knew that exercise benefits the brain, but this study goes a step further by showing that certain neurons in the hypothalamus appear to coordinate physical adaptations to training. It reinforces the idea that the benefits of exercise are not only peripheral, but also central.

[Regarding possible limitations] The results are based on animal models and should not be directly extrapolated to humans. Even so, it is very plausible that brain mechanisms facilitate or limit physical improvement, since the brain regulates metabolism, the response to exertion, and adaptation to training.

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.

The article is of good quality, with a sound experimental design. A noteworthy aspect is the link provided to a repository containing the study data, which demonstrates the transparency of the research and the researchers, and facilitates the reproducibility of the results.

It aligns with previous studies that have observed changes in the brain after exercise in rats. This study addresses a specific question regarding the effect of exercise, both single and repeated over several days, on specific brain cells in mice.

I don't consider this a groundbreaking discovery in research, but rather an incremental study, which doesn't mean it's irrelevant; on the contrary. Scientific knowledge is cumulative, and this represents another step in understanding how the brain adapts to the physical and metabolic demands of exercise. Animal models are useful in the initial stages of research, given the difficulty of studying the human brain and obtaining causal evidence.

I'm not an expert in animal research, but one limitation could be the sample size, which isn't very large. On the other hand, the main limitation is that it's a study with mice, so the conclusions shouldn't be generalized to humans. In this sense, I think it's very important that any press release on the subject makes it clear from the outset that it's an animal study—interesting and providing relevant evidence—but whose results cannot be extrapolated to people.

There's a lot of hype surrounding everything related to brain exercise, and yet, I don't think the research is consolidated with robust evidence. There's a lot of very interesting research that's adding to our knowledge, but it's premature to draw conclusions about the effects on people.

The article is interesting and of high quality. The lead author and several co-authors are known for their previous contributions to the study of neural circuits in the brain region known as the hypothalamus, which are involved in the regulation of metabolism and energy expenditure. Specifically, they discovered that neurons known as steroidogenic factor 1 (SF-1) neurons in the ventromedial nucleus of the hypothalamus are involved in the beneficial metabolic responses of skeletal muscle to physical exercise.

The novelty of this study lies in demonstrating that the activation of SF-1 neurons in the hypothalamus progressively modulates muscular and metabolic adaptation to physical exercise. In short, these neurons are activated by physical exercise and, in turn, initiate signaling that induces changes in the gene activation profile of muscle fibers, allowing them to respond better to subsequent training. It is a dynamic process in which neuronal activation progressively increases after each training session, along with the adaptation to physical exertion. If these neurons are not functional, these changes do not occur, and there is no adaptation for future exercise sessions.

Several links in the communication between muscle and SF-1 neurons, and vice versa, remain to be clarified, but the experiments are conclusive.

The authors used genetically modified mice and a wide range of physiological, imaging, and molecular techniques. Physical exercise was performed on treadmills.

This discovery may allow, in the future, for example, the enhancement of training through the activation of SF-1 neuronal circuits, or even without exercise. This would allow people with limited mobility to enjoy the brain benefits of physical activity. We know that physical activity is an essential lifestyle for maintaining and improving cognitive, emotional, and overall brain function.

To date, numerous neuroscience studies have demonstrated the beneficial effects of physical exercise on neurons. Improved respiratory, metabolic, and blood flow function is just one aspect. Factors secreted by skeletal muscle, such as BDNF (brain-derived neurotrophic factor), reach the brain, and the brain itself also secretes this and other factors that impact neuronal plasticity (increased dendritic arborization, more synaptic connections, and increased adult neurogenesis) and neuronal function (more efficient circuits, and improved cognitive and emotional functions). Interestingly, the authors detected an increase in BDNF in the ventromedial nucleus of the hypothalamus in mice after physical exercise.

These studies by the authors open a new perspective on physical exercise, suggesting that the brain controls some of the adaptive changes that occur in muscle. And it's not surprising that the signals originate in the hypothalamus, a center that regulates peripheral organs through the autonomic nervous system and is involved in energy status and vital activities such as food intake, sleep, and sexual desire.

We must consider that inhibiting these circuits doesn't completely eliminate adaptation to physical exercise, but rather reduces the response, which reaches its peak sooner and is weaker, at least in mice. Genetic predisposition is a crucial factor in the performance of elite athletes. So too is the mental strength to control exertion in endurance sports. Investigating whether the state of these neurons is involved in athletic success would confirm the relevance of this work.

The article is high-quality, very well-designed, and presents highly relevant and interesting results for the neurobiology of exercise.

It was known that exercise has direct effects on physical endurance (it was even published in 2025 that this increase from exercise is inherited and transmitted to the first generation—sedentary—when parents exercise, and the mechanisms of this inheritance were discovered), but the mechanisms by which exercise increases endurance itself in the individual exercising were still unknown.

The major novelty of this work is that it reveals that one of the essential factors/mechanisms for this is a modification that takes place in the brain. That is, the changes induced by exercise in the brain (specifically in the hypothalamus) subsequently lead to physiological/metabolic changes in the body. This is no less remarkable for being unexpected.

The limitations are threefold: we do not yet know if these brain changes also induce other known changes induced by exercise, especially in the brain (changes in cognitive ability and/or memory, for example). We also do not know if other exercise-induced mechanisms are responsible for the changes reported in this study in the hypothalamic nucleus (for example, the gut microbiota, according to our findings published last summer). And we should know more about the neural circuitry that mediates all of this (the present findings only tell us about the hypothalamic nucleus, not about what information reaches these neurons, nor where the information processed by these neurons goes afterward).