Exercise is one of the most beneficial activities that people can engage in. Regular exercise reduces the risk of heart disease, diabetes, cancer, and other health problems. It can even help people with many mental health conditions feel better.

But exactly how exercise exerts its positive effects hasn’t been well understood. And different people’s bodies can respond very differently to certain types of exercise, such as aerobic exercise or strength training.

Understanding how exercise impacts different organs at the molecular level could help health care providers better personalize exercise recommendations. It might also lead to drug therapies that could stimulate some of the beneficial effects of a workout for people who are physically unable to exercise.

To this end, researchers in the large, NIH-funded Molecular Transducers of Physical Activity Consortium (MoTrPAC) have been studying how endurance exercise and strength training affect both people and animals. The team is examining gene activity, protein alterations, immune cell function, metabolite levels, and numerous other measures of cell and tissue function. The first results, from rat studies of endurance exercise, were published on May 2, 2024, in Nature and several related journals.

Both male and female rats underwent progressive exercise training on a treadmill over an 8-week period. By the end of training, male rats had increased their aerobic capacity by 18%, and females by 16%. Tissue samples were collected from 18 different organs, plus the blood, during the training period and two days after the final bout of exercise. This let the researchers study the longer-term adaptations of the body to exercise.

Changes in gene activity, immune cell function, metabolism, and other cellular processes were seen in all the tissues studied, including those not previously known to be affected by exercise. The types of changes differed from tissue to tissue.

Many of the observed changes hinted at how exercise might protect certain organs against disease. For example, in the small intestines, exercise decreased the activity of certain genes associated with inflammatory bowel disease and reduced signs of inflammation in the gut. In the liver, exercise boosted molecular changes associated with improved tissue health and regeneration.

Some of the effects differed substantially between male and female rats. For example, in male rats, the eight weeks of endurance training reduced the amount of a type of body fat called subcutaneous white adipose tissue (scWAT). The same amount of exercise didn’t reduce the amount of scWAT in female rats. Instead, endurance exercise caused scWAT in female rats to alter its energy usage in ways that are beneficial to health. These and other results highlight the importance of including both women and men in exercise studies.

The researchers also compared gene activity changes in the rat studies with those from human samples taken from previous studies and found substantial overlap. They identified thousands of genes tied to human disease that were affected by endurance exercise. These analyses show how the MoTrPAC results from rats can be used to help guide future research in people.

“This is the first whole-organism map looking at the effects of training in multiple different organs,” says Dr. Steve Carr, a MoTrPAC investigator from the Broad Institute. “The resource produced will be enormously valuable, and has already produced many potentially novel biological insights for further exploration.”