International Business Department           Liu Bojia           September 27, 2023

  Over-nutrition and physical inactivity have become key contributors to the obesity and diabetes epidemics, and there's no doubt that exercise has a number of health benefits, such as helping to increase fat metabolism and regulating blood sugar levels. What's more, a growing body of research confirms that exercise has a significant effect in preventing cancer and dementia.

  But what happens to muscle tissue that is directly related to exercise? In a paper in Cell Metabolism, researchers from Germany found that in addition to the surface benefits of exercise that may strengthen muscles and make muscle groups more developed, it also deeply stimulates the activity of regulatory T-cells (Treg) in the muscles, a change that, in addition to making muscles grow faster, will further bring potential benefits to the whole body.

  From the data analyzed in the study, it appears that this part of the Treg in muscle exhibits a unique T cell receptor and transcriptome. Most notably, Treg in muscle expresses the transcription factor Fox3, a molecule that promotes growth.

  In addition, unlike Treg in the lymphatic system, Treg in muscle tissue, when activated, also highly expresses bimodulin, a protein belonging to the epidermal growth factor family that also contributes to tissue growth. All of this is to suggest that Treg will help muscle tissue regeneration and repair.

  In order to test this speculation, the researchers selected a group of mice and divided them into a control resting group as well as an exercise group. The mice in the exercise group possessed a roller device in their living environment, but the exercise was voluntary and the researchers would not force the mice to participate in the exercise. It was observed that after a few days of acclimatization, the mice in the exercise group had high activity levels, especially during the nocturnal active period.

  After a period of time, the researchers analyzed gene expression in the muscles of the mice's limbs, and they found that mice that participated in regular exercise had a significant increase in the expression of some genes related to muscle growth, and in addition to the dichotomous proteins that were mentioned at the beginning, the authors confirmed that interleukin 6 (IL-6) is also elevated.

  IL-6, as an immune-related factor, usually promotes inflammation under metabolic diseases such as obesity, however, in the case of exercise conditions, IL-6 released from muscle tissues plays the exact opposite role; instead of activating inflammation-related pathways, they cooperate with cellular anti-inflammatory factors and reduce the level of inflammation in the microenvironment. If the IL-6 receptors were destroyed in mice, they would not be able to reap the benefits of muscle repair and regeneration after exercise.

  In addition to the changes in the muscles themselves, the mice that participated in rollerblading under the same feeding conditions also had healthier body weights and showed a constant decrease in visceral fat mass.

  According to the researchers' long-term observations, after 4 weeks of consistent running exercise, the mice were able to largely maintain the positive effects they had gained even after 2 consecutive weeks of rest, and did not return to their pre-exercise baseline levels until after 4 weeks of rest. They suggest that this is a manifestation of muscle immune memory, and that as long as exercise is maintained, the benefits can be retained even if an occasional bout of rest is desired.

  The researchers point out that some anti-inflammatory therapies work against the IL-6 receptor, but users may experience muscle weakness as a side effect, which makes sense in light of the new study's findings. They believe that more targeted obesity and muscle damage therapies could be developed for Treg in the future, and could also help balance the relationship between immunity and metabolism.