Physiology: neurons, hormones and obesity.

Studies that have mapped the connections between neurons in the brain, gain insight into the regulation of appetite and metabolism. The ARC and VMH has long been thought of as satiety centers. Studies that investigate the role of the arcuate nucleus in the hypothalamus, in regulating appetite and metabolism, have targeted two chemically identified neuronal types within the ARC: anorexigenic pro-opiomelanocortin (POMC) neurons and orexigenic neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons. The melanocortin α-melanocyte stimulating hormone (α-MSH, a biologically active peptide produced in POMC neurons) serves as an agonist, whereas AgRP is an inverse agonist at the anorectic melanocortin receptors (MC3R and MC4R) in the central nervous system. NPY elicits its physiological effects via differential activity at the G-protein coupled NPY receptors (NPY1R, NPY2R, NPY4R, and NPY5R) independent of melanocortin receptors [11]. Notably, although there are only a few thousand POMC and NPY/AgRP neurons within the arcuate nucleus [7], α-MSH and NPY/AgRP released from these neurons have potent effects on food intake and metabolism, respectively.
“ POMC neurons release the anorexigenic peptide α-melanocyte stimulating hormone (α-MSH), whereas NPY/AgRP neurons release the orexigenic peptides NPY/AgRP and GABA at their target nuclei in brain and spinal cord. Arcuate POMC and NPY/AgRP neurons express receptors for peripheral (e.g., leptin, insulin, and ghrelin) and central (e.g., melanocortin, NPY, GABA, and serotonin) signals. “ The electrical activity (resting membrane potential and/or action potential firing frequency) of POMC and NPY/AgRP neurons may be acutely modulated by these signals, which is believed to affect the release of α-MSH and NPY/AgRP/GABA to their target neurons. In the arcuate nucleus there is a local circuit in which POMC neurons receive GABAergic (inhibitory) input from NPY/AgRP neurons. The central melanocortin pathway involves arcuate POMC