(A) Leptin and insulin bind to their specific receptors to regulate brain functions. Leptin and insulin activate POMC neurons and inhibit AgRP/NPY neurons to suppress feeding behaviour. Ghrelin on the other hand, activates AgRP/NPY neurons to stimulate feeding behaviour. Leptin and insulin also regulate neuronal functions within brain regions that are important components for cognition and reward behaviours such as the hippocampus and VTA. (B) Neuromodulators including peptide hormones regulate both excitatory and inhibitory synaptic functions. The modulatory functions can be both presynaptic and postsynaptic origins. Hormones such as insulin, leptin and ghrelin bind to their corresponding receptors and activate second messenger cascades to influence synaptic function. Note that the signalling cascades depicted in the postsynaptic compartment also apply to the presynapse. Abbreviations: CAM, cell-adhesion molecules (e.g. neurexins and neuroligins); Cart, cocaine- and amphetamine-regulated transcript; GABAR, GABA receptors; GluR, glutamate receptors including both NMDAR and AMPAR; LDCV: large-dense core vesicle; MEK, MAPK/extracellular-signal-regulated kinase kinase; PKC, protein kinase C; PLC, phospholipase C; PSD, postsynaptic density; SV, synaptic vesicle X1R, neuropeptide X1 receptor.