Established in 2016, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a national research group designed to discover and perform preliminary characterization of the molecular transducers that underlie the effects of physical activity in humans.

During the symposium The Molecular Transducers behind the Benefits of Physical Activity,  a panel of MoTrPAC principal investigators provided an update on consortium activities and discussed how early data from animal studies is setting the stage for human studies.

The session, which was originally presented Friday, June 25, can be viewed by registered meeting attendees at ADA2021.org through September 29, 2021. If you haven’t registered for the Virtual 81st Scientific Sessions, register today to access all of the valuable meeting content.

Wendy M. Kohrt, PhD, Distinguished Professor of Medicine and the Nancy Anschutz Chair in Women’s Health Research, University of Colorado Anschutz Medical Campus, provided an overview of the consortium. Dr. Kohrt serves as chair of the MoTrPAC Steering Committee and principal investigator of the MoTrPAC clinical site at the University of Colorado.

MoTrPAC is comprised of four components—clinical sites, animal study sites, chemical analysis sites, and omics sites—at various institutions across the country.

“The overarching goal of MoTrPAC is interesting because this isn’t a typical NIH (National Institutes of Health) trial, in that we’re partnering a clinical trial with extensive omics characterization of the molecular signals that are turned on or off by physical activity. So, we don’t have a primary hypothesis and we don’t have a primary outcome,” Dr. Kohrt said. “Our goal is, rather, to deliver a product to the scientific community that will be what we refer to as a comprehensive ‘map’ of the molecular changes that occur in response to physical activity.”

Understanding those changes, she said, may provide insights into the molecular mechanisms that are responsible for the health benefits of physical activity.

“We also want to determine how these signals are affected by a variety of parameters, such as age, sex, body composition, fitness level, race, ethnicity, and other parameters,” Dr. Kohrt said. “The long-term goal is to deliver this molecular map—this very rich dataset—to the scientific community so that it can be used to facilitate further research in this area.”

Karyn A. Esser, PhD, Professor of Physiology and Functional Genomics and Associate Director, Myology Institute, University of Florida College of Medicine, provided an overview of the consortium’s preclinical animal studies conducted at six sites. Dr. Esser serves as chair and principal investigator of the MoTrPAC Preclinical Animal Studies Sites (PASS).

Among the key challenges in establishing the animal studies sites was standardizing protocols and methods, she said.

“The first part was to work within the consortium with our colleagues to develop a treadmill exercise intervention for the preclinical animals, which are rats, but took into account the plans that were on the docket for the human clinical studies,” Dr. Esser said. “So, our goal was to try to harmonize between the animal studies and the humans as best we could.”

Additional considerations included developing standardized tissue collection protocols, as well as coordination of animal control factors such as housing, feeding, and light-dark cycles, she noted. PASS phase 1 includes both acute response to exercise studies and chronic exercise training studies.

Early data from the PASS phase 1 training study suggests robust cardiovascular responses to chronic treadmill exercise in both male and female rats, Dr. Esser said. Additionally, she noted that the effect of treadmill exercise on body composition varied between sexes, with an increased loss of body fat in males and an induced shift in fiber type in females.

“What the phenotyping data from the training study established is that the training did what we all expected it would do,” Dr. Esser said. “We now have some timelines for changes that provide a little bit more rigor in terms of understanding how soon these changes are occurring when we train, and obviously the inclusion of both males and females at the same time gives us much more power to look for sex-specific differences.”

Data collection and analyses from the phase 1 studies measuring acute response to exercise is ongoing.

K. Sreekumaran Nair, MD, PhD, the Dr. Richard F. Emslander Professor in Endocrinology and Distinguished Investigator, Mayo Clinic, provided an overview of the MoTrPAC omics approach to studying responses to acute exercise and training. Dr. Nair is principal investigator of the MoTrPAC Chemical Analysis Sites at the Mayo Clinic.

MoTrPAC investigators aim to use multi-omics approaches to study the difference in responses and effects of acute exercise as opposed to chronic or training exercise, Dr. Nair noted.

“In both situations we want to see the local effect—and by local I mostly mean skeletal muscle—and multiorgan effects of exercise,” he said. “When you do exercise, cardiac output increases and blood circulation to every organ increases.”

Previous and ongoing studies are providing new insight regarding the beneficial effects of exercise training on brain functions, including increases in oxidative metabolism, mitochondrial efficiency, and glucose uptake in the brain, Dr. Nair said.

“The brain is a key organ impacted by and regulating multiorgan responses to exercise,” he continued. “The brain has impact on all body functions, sending signals to the rest of the body, so the question we need to address is whether this can explain some of the changes occurring in response to exercise.”

For more information and to access the MoTrPAC Data Hub, visit MoTrPAC.org.