ARCAgRP/NPY Neuron Activity Is Required for Acute Exercise-Induced Food Intake in Un-Trained Mice.

Wyatt Bunner,Zhijian Rao,Peixin Li,Taylor Landry,Brenton Thomas Laing,Hu Huang,Yuan Yuan

doi:10.3389/fphys.2020.00411

Abstract

While much is known about the role of agouti-regulated peptide/neuropeptide Y (AgRP/NPY) and pro-opiomelanocortin (POMC) neurons to regulate energy homeostasis, little is known about how forced energy expenditure, such as exercise, modulates these neurons and if these neurons are involved in post-exercise feeding behaviors. We utilized multiple mouse models to investigate the effects of acute, moderate-intensity exercise on food intake and neuronal activity in the arcuate nucleus (ARC) of the hypothalamus. NPY-GFP reporter mice were utilized for immunohistochemistry and patch-clamp electrophysiology experiments investigating neuronal activation immediately after acute treadmill exercise. Additionally, ARCAgRP/NPY neuron inhibition was performed using the Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system in AgRP-Cre transgenic mice to investigate the importance of AgRP/NPY neurons in post-exercise feeding behaviors. Our experiments revealed that acute moderate-intensity exercise significantly increased food intake, ARCAgRP/NPY neuron activation, and PVNSim1 neuron activation, while having no effect on ARCPOMC neurons. Strikingly, this exercise-induced refeeding was completely abolished when ARCAgRP/NPY neuron activity was inhibited. While acute exercise also increased PVNSim1 neuron activity, inhibition of ARCAgRP/NPY neurons had no effect on PVNSim1 neuronal activation. Overall, our results reveal that ARCAgRP/NPY activation is required for acute exercise induced food intake in mice, thus providing insight into the critical role of ARCAgRP/NPY neurons in maintaining energy homeostasis in cases of exercise-mediated energy deficit.

Highlights

The hypothalamus in the CNS is critical to the control of energy homeostasis, with the arcuate nucleus (ARC) and the sub-populations of neurons contained within it being especially important in fulfilling this role (Knner et al, 2009)
There were no differences in the number or activation of ARCPOMC expressing neurons in the exercise group compared to the sedentary group (Figures 1A–D)
In this study we investigate the effect of an acute bout of exercise on the activity of ARCAgRP/NPY and their adjacent ARCPOMC-expressing neurons in the hypothalamus, as well as the role of ARCAgRP/NPY neuron activation in the associated feeding response post-exercise

Summary

Introduction

The hypothalamus in the CNS is critical to the control of energy homeostasis, with the arcuate nucleus (ARC) and the sub-populations of neurons contained within it being especially important in fulfilling this role (Knner et al, 2009). Activation of AgRP/NPY neurons in the ARC by either chemical or optogenetic stimulation results in an immediate and robust increase in food intake (Aponte et al, 2011; Krashes et al, 2011), while ablation of AgRP/NPY neurons results in decreased food intake, which, if not reversed, can lead to starvation in adult mice (Gropp et al, 2005; Wu et al, 2009). These evidences highlight the novel but distinct roles of these two ARC neuron subpopulations in regulating food intake

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