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.
The proposed studies will greatly increase our understanding of the acute mechanisms underlying GLP-1 dependent regulation in the brain. The study findings will allow us to learn how to better co-opt the mechanisms by which GLP-1 and exercise promotes improvements to metabolism. Moreover, these data are likely to have clinical implications for diabetes research as GLP-1 receptor agonists are common therapeutics in diabetes treatment/management.
