Physical activity provides multiple metabolic benefits, including improved insulin sensitivity and body composition. Within the brain, less is known about the effects of exercise to acutely alter synaptic/cellular properties and how these effects contribute to altered metabolism. In the current proposal, we have found that CNS derived GLP-1 neurons are activated in response to exercise. Moreover, GLP-1 and GLP-1 mimetics mimic the effects of exercise on arcuate melanocortin neurons. Collectively, these data support the hypothesis that an NTS GLP-1 to arcuate POMC circuit is activated in response to exercise. We will identify cellular mechanisms through which exercise activates GLP-1 and melanocortin neurons. We will also determine a role for these acute/chronic cellular mechanisms to regulate metabolism.