Insulin, leptin, serotonin and melanocortin pathways all meet in the ARC

Or in the longer version that insulin, leptin, serotonin and melanocortin pathways all meet in the arcuate nucleus of the hypothalamus (ARC).

Details?

Serotonin and melanocortin pathways, at least their parts, are already well established. In the ARC, serotonin acts via Gq-coupled serotonin 2C receptors (5-HT2CRs) on neurons that co-express cnorectic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript peptide (CART). Additionally, also in the ARC, serotonin simultaneously acts via Gi-coupled inhibitive serotonin 1B receptors (5-HT1BRs) on neurons that express orexigenic agouti related peptide (AgRP). These stimulations decrease the likelihood of AgRP release at downstream melanocortin 4 receptors (MC4Rs) and increase the likelihood of release of the anorexic alpha-melanocyte stimulating hormone (alpha-MSH) at the MC4Rs. We also know that MC4Rs are critical downstream mediators of this serotonin-induced anorexia, particularly those in the paraventricular nucleus of the hypothalamus (PVH).

POMC and AgRP neurons also express leptin receptors. Leptin, similarly to serotonin, stimulates anorexic POMC neurons and inhibits orexigenic AgRP neurons to induce anorexia, i.e. reduction of food intake.

Insulin also stimulates the ARC neurons, which express insulin receptors.

Significance?

This is all important as it highlights that brain is an important regulator of how much food we eat and, secondly, because it shows the immense complexity of the neural pathway that are involved in this process.