Fig. 6
From: Signaling pathways in obesity: mechanisms and therapeutic interventions
Melanocortin pathway in obesity pathogenesis. The melanocortin pathway consists of POMC; melanocortin receptors MC1R-MC5R; and agouti and AgRP. POMC/CART neurons in ARC are stimulated by anorexigenic hormones in the third ventricle like GLP-1, leptin, CCK, PYY, and 5-HT, while suppressed by orexigenic hormones like Ghrelin, ILP-5, and asprosin. Upon stimulation, POMC/CART neurons secrete POMC including α-MSH and ACTH. α-MSH is released into the PVN. By interacting with MC4R, α-MSH activates PVN neurons and displays anti-obesity effects by inhibiting adipogenesis, promoting lipolysis, inducing WAT browning, reducing food intake, and improving insulin sensitivity. ACTH released by POMC/CART neurons actions on adipocytes directly by binding to MC2R, further promoting lipolysis. However, these effects can be abolished by AgRP, which is the endogenous antagonist of POMC and is secreted by AgRP/NPY neurons in ARC. Conversely, AgRP/NPY neurons can be stimulated by orexigenic hormones in the third ventricle but inhibited by anorexigenic hormones. Notably, POMC/CART and AgRP/NPY neurons interact mutually. NPY receptor Y1R is expressed in POMC/CART neurons and its activation inhibits POMC neurons in the ARC. In contrast, MC3R expressed in AgRP/NPY neurons seems to increase food intake in an “AgRP circuitry”-dependent manner
