Figure 2. Regulation of food intake at the level of hypothalamus (arcuate nucleus). The orexigenic message of ghrelin enters the brain via the vagus nerve and causes local release of ghrelin from ghrelin-containing neurons which in turn binds to its receptor on Npy/AgRP/GABA neurons, giving rise to an increased production of Npy and AgRP as well as an increased firing rate of these neurons. The consequences are twofold: firstly, inhibition of firing of POMC/CART neurons (through GABA) and secondly stimulation of firing of the orexigenic neurons in the LHA/PFA region (through Npy and AgRP). A predominant orexigenic signal ensues.Insulin and leptin directly diffuse into the arcuate nucleus and they bind to their receptors on both Npy/AgRP/GABA and POMC/CART neurons. However, they have opposing effects on these neurons. Leptin and insulin promote expression of α-MSH (anorexigenic) but suppress expression of Npy and AgRP (orexigenic). As a consequence a predominant anorexigenic signal ensues.Messenger abbreviations : Npy, neuropeptide Y, AgRP, agouti-related protein, GABA, gamma-amino butyric acid; α-MSH, alpha-melanocyte stimulating hormone=melanocortinReceptor abbreviations : GSHR, growth hormone-secretagogue receptor=ghrelin receptor; LepR, leptin receptor; INSR, insulin receptor; Y1R, Npy receptor, MC4R, melanocortin-4 (α-MSH) receptor.