Exercise intensity differentially modulates systemic molecular responses and predicted interorgan communication in humans

Exercise is recognized as a first-line lifestyle therapy for many cardiometabolic diseases, including obesity, type 2 diabetes, and hypertension. Despite the abundant health-promoting effects of exercise, in-depth characterization of circulatory factors mediating these benefits remain understudied in humans. Moreover, how different modes of exercise uniquely regulate these processes is unclear. Here, we address these questions by conducting a multi-cohort human exercise intervention, incorporating sprint-interval exercise (SIE), moderate-intensity exercise (MIE), and treadmill exercise to exhaustion to analyze intensity-dependent regulation of adipocytes and bulk adipose tissue. We find that exercise intensity uniquely influences the plasma proteome and plasma metabolome, and culturing primary human adipocytes with these plasma samples results in robust intensity-dependent transcriptome changes. We confirm many of these genes are similarly regulated by intense exercise in vivo, via RNA-sequencing of bulk adipose tissue following treadmill exercise to exhaustion. These findings underscore intensity-dependent regulation of adipose tissue following exercise.