While insulin has been proposed to benefit cognition, the effect of exercise on neuronal insulin signaling in humans is unclear.<h4>Purpose</h4>We tested the hypothesis that a single bout of aerobic exercise would raise insulin signaling mediators from plasma-derived neuronal extracellular vesicles (nEVs).<h4>Methods</h4>Fifteen sedentary adults with obesity (12F; ~56y; ~31 kg/m<sup>2</sup>) completed an evening rest and acute exercise condition (70% maximal oxygen consumption (VO<sub>2</sub>max)) in a randomized, counterbalanced order. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.