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Study pinpoints molecular changes in rats after exercise

Two girls run on a track.

A new study from a large team that included UF Health researchers that used laboratory rats as models shows that endurance exercise creates significant physiological changes in the body. The study moves next to human subjects. (Getty images)

GAINESVILLE, Fla. — Lab rats and their exercise treadmills may hold the molecular answer to the health benefits of physical activity for humans.

As part of the National Institutes of Health-funded Molecular Transducers of Physical Activity Consortium, or MoTrPAC, UF Health researchers have published preclinical work in Nature that expands understanding of the biology behind exercise.

Pooling scientists from across physiology, genetics and more through 23 national research institutions, MoTrPAC aims to pin down molecular changes that occur in the human body during physical activity that lead to better health outcomes, such as lowering risk for conditions such as diabetes, cancers and heart disease.

A principal investigator on the project, Karyn Esser, Ph.D., chair of the department of physiology and aging at the UF College of Medicine, leads the UF preclinical site, with the other two sites housed at the University of Iowa and Harvard University.

The health benefits of physical activity are well-documented: Exercise lowers the probability of some cancers and neurodegenerative diseases while improving heart and immune system health. Yet questions remain about why.

“It’s a no-brainer — we know being active is healthy. But in terms of the molecular mechanisms that support health throughout our body, it’s not clear,” Esser said. “We haven’t known all the organs involved and we haven’t known all the pathways and molecular targets of exercise. The goal of this first series of studies was really descriptive but very deep.”

Setting out to build a molecular map, Esser and her UF cohort studied changes in 19 tissue types in male and female rats after one, two, four and eight weeks of exercise training. The project moved beyond evaluating skeletal muscle and bone tissue, delving into effects on the lungs, spleen, intestines and more.

The treadmill trainings were designed to mimic the endurance training humans might undertake during ongoing MoTrPAC clinical research studies. The rats ran on their treadmills five mornings a week, for 40 minutes to an hour. After each workout, they were replenished with food, drink and rest.

Overall, 35,439 biological features were shown to change after exercise training and those represented changes in proteins, genes and metabolites across all tissues and timepoints. Simply put, all tissues and organs responded to exercise training in male and female rats and these changes were found across many different molecular markers.

The scientists also found changes that might apply to human disease, including significant molecular adaptations in the small intestines and colons of the male and female rats following the eight- week training that suggest exercise benefits for irritable bowel syndrome and gut inflammation. They also discovered that about half the mitochondrial genes in the adrenal glands underwent changes in expression in response to endurance training. And the work highlighted sex-specific differences in response to exercise training, such as the female adrenal glands showing opposite changes in hormonal pathways compared with males.

The NIH collaboration is ongoing, with human trials to study exercise’s health benefits. For now, the work of UF Health researchers and other contributors can be found in the public MoTrPAC data repository to enable further discoveries.

“Exercise is an incredibly potent physiological stimulus for human health,” Esser said. “There’s a great need to understand its potential for health maintenance and disease prevention for both intervention studies but also to support future drug design and therapeutics.”

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