Conserved multitissue transcriptomic adaptations to exercise training in humans and mice

Physical activity is associated with beneficial adaptations in human and rodent metabolism. We studied over 50 complex traits before and after exercise intervention in middle-aged men and a panel of 100 diverse strains of female mice. Candidate gene analyses in three brain regions, muscle, liver, heart, and adipose tissue of mice revealed genetic drivers of clinically relevant traits including volitional exercise volume, muscle metabolism, adiposity, and hepatic lipids. Although ~33% of genes differentially expressed in skeletal muscle following the exercise intervention were similar in mice and men independent of BMI, responsiveness of adipose tissue to exercise-stimulated weight loss appears impacted by species and underlying genotype. We leveraged genetic diversity to generate prediction models of metabolic trait responsiveness to volitional activity offering a framework for advancing personalized exercise prescription. Finally, we make the human and mouse data publicly available via user-friendly web-based application to enhance data mining and hypothesis development. Overall design: Expression profiling by RNA-Seq for five tissues (gonadal white adipose, heart, liver, quadriceps, brown adipose) in 50 inbred mouse strains under sedentary and exercised conditions