Why is exercise good for you?

Researchers at AdventHealth in Orlando seek clues

Researchers at AdventHealth in Orlando soon will start recruiting volunteers for what’s considered the largest federally-funded study on exercise, aiming to discover the molecules and pathways that are involved in the health benefits of physical activity.

“We know that [exercise] reduces diabetes risk and cancer risk and body fat,” said Dr. Bret Goodpaster, a senior investigator at the Translational Research Institute at AdventHealth in Orlando, formerly known as Florida Hospital. “But we don’t know how it works. In a nutshell, this project is trying to discover the how and the why of the benefits of exercise.”

The institute is one of about two dozen hospitals and universities across the nation to get a portion of a $170 million grant from the National Institutes of Health to develop a map of molecular mechanisms that are linked to physical activity. The study is called The Molecular Transducers of Physical Activity in Humans, or MoTrPAC, aptly pronounced MotorPack.

The study has no specific hypothesis. Rather, it’s a discovery project. And it’s significant because, in the end, it will produce a large open database that will give researchers the ability to conduct more targeted studies in the next decade about why people respond differ-

ently to exercise, why lack of exercise can be harmful to our health and what role gender plays in how we respond to exercise.

“So the hope is to get an initial understanding of what molecules and pathways are involved in the benefits of physical activity,” said Dr. Karyn Esser, professor and associate director of the Myology Institute at the University of Florida, which is one of the participating sites in MoTrPAC. “By finding what does change and what doesn’t change, we can start honing the focus in where the important mechanisms lie.”

Dr. Peter Crawford, division director and vice chair for research at the Department of Medicine at the University of Minnesota, said he’s most interested in data that will emerge about the molecular interaction between organs and potential clues about why lack of physical activity could be harmful to our health or play a role in aging.

“It’s not known if the same pathways [involved in response to exercise] are the ones that go the wrong way in a sedentary life,” said Crawford, who isn’t involved in MoTrPAC. “Just because we know exercise is good for you, it doesn’t mean that we know the whole story.”

The NIH launched MoTrPAC in 2015, eventually selecting more than 20 institutions across the nation to perform various aspects of the research, including animal and human studies as well as cuttingedge sequencing and chemical analyses.

“In my opinion, this is the most complicated project that NIH has ever funded, for a lot of reasons,” said Goodpaster, the principal investigator of MoTrPAC at the Translational Research Institute at AdventHealth. “It puts TRI on the map as a real player in being able to conduct these types of studies.”

AdventHealth’s institute and several other institutions across the country will kick off the human studies in the spring, enrolling a diverse group of participants, including children, older adults and various racial and ethnic groups, with equal numbers of men and women.

From 1,500 to 2,000 participants, including about 200 volunteers in Orlando, will take part in a 12-week exercise program — either aerobic or resistance exercise — during which researchers will collect blood, urine, fat and muscle samples before and after the workout session.

The animal research sites, including UF, have already started studying the impact of treadmill exercise in rats. They collect samples from the rats’ organs, especially the ones that aren’t easy to study in humans — like the heart, lung and the brain. Some of the samples come from rats that run just once on the treadmill. Other rats are studied after an 8-week exercise program.

Frozen samples from animal and human study sites are then sent to several institutions that will conduct different types of analyses to identify changes in biological molecules, proteins and genes.

“I’m most excited to see the breadth of the impact of exercise across organ systems,” Esser said.

She and her UF team soon will ship the first batch of samples for analysis and will have the results within six months to a year. “We should have exciting discoveries in the next year,” Esser said.

MoTrPAC will also fund a user-friendly data center for researchers who want to use the database to conduct their own investigations.

A project of this scope only became possible in recent years because of advancements in technology and the ability to share big data. Another driver for the study is the medical community’s shift in focus from treatment to prevention.

“These kinds of studies have been applied to different diseases, but exercise is different because it’s preventive,” said Esser, an avid runner. “It has taken time for the biomedical community to embrace the benefits of exercise for more than caloric expenditure and looking good and that it actually plays a fundamental role in the health of human beings.”

Based on revelations from the project, physicians could one day prescribe personalized exercise regimens.

Goodpaster, who ran three half-ironman triathlons last year, added that “we could perhaps develop a non-exercise intervention or therapy that mimics at least some of the effects of exercise.”