Physical activity is well-recognized as an important contributor to human health and well-being. However, the molecular mechanisms that mediate the systemic benefits of physical activity have remained largely mysterious. I have identified a metabolite, Lac-Phe, that is robustly stimulated by physical activity in both mice and humans. Functional studies reveal Lac-Phe to be a periphery-to-brain-signal that suppresses appetite and obesity. I aim to understand the anorexigenic activity of Lac-Phe by elucidating the structural characteristics required for appetite suppression. This is important because it will provide potential therapeutic avenues for “capturing” the molecular transducers of physical activity for improving human health.