The current
obesity epidemic and lack of efficient
therapeutics demand a clear understanding of the mechanism underlying
body weight regulation. Despite intensive research focus on
obesity pathogenesis, an effective therapeutic strategy to treat and cure
obesity is still lacking. Exciting studies in last decades have established the importance of hypothalamic
agouti-related protein-expressing neurons (AgRP neurons) in the regulation of
body weight homeostasis. AgRP neurons are both required and sufficient for feeding regulation. The activity of AgRP neurons is intricately regulated by nutritional
hormones as well as synaptic inputs from upstream neurons. Changes in AgRP neuron activity lead to alterations in the release of mediators, including
neuropeptides Neuropeptide Y (NPY) and AgRP, and fast-acting
neurotransmitter GABA. Recent studies based on mouse genetics, novel optogenetics, and designer receptor exclusively activated by
designer drugs have identified a critical role for
GABA release from AgRP neurons in the parabrachial nucleus and paraventricular hypothalamus in feeding control. This review will summarize recent findings about AgRP neuron-mediated control of feeding circuits with a focus on the role of
neurotransmitters. Given the limited knowledge on feeding regulation, understanding the action of
neurotransmitters may be a key to unlock neurocircuitry that governs feeding.