AgRP neuron activity is required for acute exercise-induced feeding

Abstract

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.