The University of Michigan’s Molecular Transducers of Physical Activity (MoTrPAC) Chemical Analysis Site (MiCAS) has been providing large-scale, high-quality untargeted metabolomics analysis in collaboration with the MoTrPAC consortium. In this renewal, MiCAS will continue to provide metabolomics analysis by reversed- phase chromatography with ionization in both the positive and negative mode and by ion-pairing chromatography in the negative mode. In addition, MiCAS will perform steroid analysis for baseline samples for each enrollee. These studies will be led by a team of chemists, spectroscopists, computer scientists and statisticians in the Michigan Metabolomics Core which is part of the University of Michigan’s Biomedical Research Core Facilities. During the preclinical phase and the initial human phase, MiCAS investigators carried out analysis of thousands of sample derived from animals and people recruited by the MoTrPAC Clinical Centers. In the final phase of the study, MiCAS will continue to provide analysis of blood, skeletal muscle and adipose tissue on the ‘PostCOVID’ sample collection expected to be 1980 subjects enrolled in four related clinical studies are ongoing. The largest is assessing sedentary adults randomly assigned to one of three groups: Endurance Exercise (EE; N=840), Resistance Exercise (RE; N=840), or a control group with no exercise (N=300). The participants in the intervention groups are scheduled to undergo a single acute testing bout of either EE or RE at the beginning and end of the study of a 12-week training period which is accompanied timed collection of blood, skeletal muscle, and adipose tissue. Control group participants undergo similar biospecimen collections before and after 12 weeks of usual activity. Additionally, molecular changes in response to acute exercise are being assessed in 300 highly active (HA) adults, with N=150 participating in EE and N=150 in RE. These individuals receive a single testing bout of either EE or RE, depending on their usual training modality. Finally, in a pediatric study, both highly active (HA; N=50) and low active (LA; N=270) children and adolescents will be analyzed in a cross-sectional study. A randomized 12-week EE training study is being conducted with LA children and adolescents with N=120 participants randomized to an EE group and N=50 in a control group. Adults and children will be sampled according to the approved MoTrPAC Tissue Analysis Plan. MiCAS investigators will continue to develop new approaches to analyze metabolomics data, including a novel approach to name the thousands of unknown molecular features found in untargeted metabolomics which may serve as molecular transducers. MiCAS personnel also lead and participate in all activities of the MoTrPAC consortium, including serving on committees, participating in consortium meetings, and participating in data analysis, integration of data across ‘omics types, writing and editing manuscripts arising from the consortium’s activities.

The Molecular Transducers of Physical Activity (MoTrPAC) project will define the molecular changes that occur during exercise and following exercise training. The identification of which molecules change with exercise and training may allow us to find ways to enhance or mimic the broad beneficial effects of exercise on a person’s health.