AgRP neuron activity is required for acute exercise-induced feeding

While much is known about the role of neuropeptide Y/agouti-regulated peptide (NPY/AgRP) and pro-opiomelanocortin (POMC) neurons to regulate energy homeostasis , little is known about how forced energy expenditure , such as exercise , modulates these neurons and how this relates to energy intake. Therefore , we investigated the effects of acute exercise on neuronal activity in the arcuate nucleus (ARC) of the hypothalamus. To accomplish this , we utilized immunohistochemistry and patch-clamp electrophysiology experiments on NPY-GFP transgenic mice immediately after an acute bout of treadmill exercise. Due to the ability of NPY/AgRP and POMC neurons to mediate energy homeostasis , food intake studies were also performed immediately after an acute bout of treadmill exercise. AgRP-Ires-cre transgenic mice were used to induce loss in AgRP neuronal activation by bilaterally injecting an inhibitory cre-recombinase-dependent Adeno Associated Virus (AAV-hM4Di-mCherry) to assess AgRP neurons in food intake post-exercise. While we observed no difference in activation in POMC neurons , immediately after exercise , activation in ARC NPY/AgRP neurons is significantly increased compared to the sedentary control group; further confirmed by electrophysiology recording showing a significant increase in firing rate in NPY/AgRP neurons after acute exercise. Food intake was significantly increased immediately after an acute bout of exercise. This exercise-induced food intake was abolished when AgRP neuron activation was inhibited. Neuronal inhibition of AgRP neurons had no effect of hypothalamic paraventricular nucleus (PVN) activation immediately after a bout of acute exercise. Our results demonstrate NPY/AgRP activation is critical for acute exercise induced food intake in mice , thus providing insight into the subtle exercise induced response to facilitate energy replacement