Identification of >150 Novel Exercise-Regulated Circulating Factors

Physical activity is critical for the prevention and treatment of type 2 diabetes and other chronic diseases. We hypothesize that exercise training alters the circulating milieu, and these factors mediate some benefits of exercise. To discover novel circulating factors we used an integrated metabolomic and proteomic approach. Male S-D rats (n=8/group) were trained for 3 weeks by voluntary wheel running (6.1 ± 2.4 km/day) or sedentary. Plasma was collected 6 hours after removal from wheel cages and analyzed by non-targeted metabolomics and SomaScan proteomics. Trained rats had lower body and fat weights, lower fasting insulin, and improved glucose tolerance vs. sedentary (all p<0.05). Metabolomics detected 273 metabolites and training significantly increased 9 and decreased 13 (p<0.05). Proteomics detected 1310 proteins and training increased 94 and decreased 35 (p<0.05). Integrated analysis combining metabolomic and proteomic data showed training significantly altered pathways of glucose metabolism, VEGF signaling, and heat stress. Correlation analyses between metabolic parameters and metabolites or proteins were also done to identify novel factors that may function to improve health (Table). Of the training-regulated metabolites and proteins, >90% are previously unknown exercise factors. These factors are potential therapeutic targets and provide unique insight into the complex changes that occur with exercise training.