What does exercise do to the body? There are many health benefits we know about, but what happens on a molecular, or even a cellular, level? What happens to other organs besides our muscles, heart, and lungs? Is endurance training or resistance training better for, say, the kidneys? All these questions and more are being explored under an enormous project involving nineteen different institutions, including the University of Iowa, inside the lab of Sue Bodine, PhD.
The Molecular Transducers of Physical Activity Consortium, or MoTrPAC, is the largest study of the impact of exercise ever conducted. Under the direction of NIH Director Francis Collins, MD, PhD, and funded from the NIH common fund, researchers around the country are approaching the effort to draw a molecular map of exercise simultaneously from an array of angles. Eleven clinical sites will produce samples from 2,600 male and female humans of all ages before, during, and after strictly measured amounts and types of exercise. Meanwhile at three other sites, preclinical animal studies will perform similar amounts of testing, but generating far greater amounts of samples. Bodine, a professor in endocrinology and member of the UI’s Fraternal Order of Eagles Diabetes Research Center, has been leading one of the three animal testing sites in MoTrPAC.
Beginning with the endurance, or chronic, exercise evaluations, Bodine and her colleagues established a control group of rats and another of male and female rats that were given increasing distances to run. “We were looking for improvements in exercise capacity,” Bodine said. She also described the array of chemical analyses that the harvested tissue samples would go through, “the different omic analyses, proteomics, metabolomics, genomics. So, transcriptomics.” This complete set of RNA transcripts will provide a wealth of data to compare against the control group.
“We have treadmills,” Bodine said, describing the process by which the rats are exercised. “But there’s always a small percentage of animals that refuse to run, just like humans.” After identifying their maximum running speed, Bodine said that 70 percent of that speed is set, just as in the human study, “at a speed that’s comfortable for them.” Over time, the speed is increased as is the grade of incline on which they run and the amount of time that they run each day, again matching the human trial.
The project began in 2017, first in a year of planning and coordination across the many sites, devising protocols each site would follow. Animal studies began in 2018 and the three preclinical animal sites, including Bodine’s, have since sent off their tissues from the chronic trials. The next phase will be the resistance exercise trials, which will follow similar protocols as the endurance. In the resistance study, the rats will climb ladders with increasing amounts of weight attached to them. And, just as in their first exercise trials, a similar set of samples from 19 different organs will enter the biorepository for the omics analysis.
MoTrPAC “will generate a significant amount of data,” Bodine said. It will all go to one bioinformatics site at Stanford University that will assemble the data, both from the human and animal studies, some of which is already available to the public for mining. “We’re also creating a biorepository of tissue that other people can study.”
The analysis of this volume of data will go on for years, Bodine said. And where past studies have only looked at muscle or blood, this study will look at a variety of organs–kidneys, brain regions, lungs, adrenal glands–all to get a better sense of how these organ systems respond to a variety of exercise scenarios, whether acute or chronic. With greater amounts of understanding of how systems and even cells are affected, the possibility of prescribing certain kinds of exercise tailored to an individual’s unique needs is increased.
Once an understanding of exercise under ideal circumstances is better understood, the next step may be to study exercise in various settings of disease. How, for example, might cardiovascular exercise be a better option for someone with diabetes than weight training? “What can come out of MoTrPAC,” Bodine said, “is a better understanding of exercise and how to prescribe to improve health, but also how to prevent or treat certain diseases. I imagine that there will be years of other studies that come out of this.”
The “marker paper” outlining the consortium’s aims, protocols, and organizational structure was published late last month in Cell.