Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance

Abstract
Neurons expressing Agouti-related protein (AgRP) and neuropeptide Y (NPY) in the hypothalamus are involved in regulation of feeding and body weight, but genetic disruption of AgRP and NPY have little effect on energy homeostasis. A new study from Tong et al. shows that the energy homeostasis function is mediated through their GABAergic transmission. The physiologic importance of GABAergic neurotransmission in hypothalamic neurocircuits is unknown. To examine the importance of GABA release from agouti-related protein (AgRP) neurons (which also release AgRP and neuropeptide Y), we generated mice with an AgRP neuron–specific deletion of vesicular GABA transporter. These mice are lean, resistant to obesity and have an attenuated hyperphagic response to ghrelin. Thus, GABA release from AgRP neurons is important in regulating energy balance.