The melanocortin pathway and control of appetite-progress and therapeutic implications

The Journal of Endocrinology
Giulia Baldini, Kevin D Phelan

Abstract

The initial discovery that ob/ob mice become obese because of a recessive mutation of the leptin gene has been crucial to discover the melanocortin pathway to control appetite. In the melanocortin pathway, the fed state is signaled by abundance of circulating hormones such as leptin and insulin, which bind to receptors expressed at the surface of pro-opiomelanocortin (POMC) neurons to promote processing of POMC to the mature hormone α-melanocyte-stimulating hormone (α-MSH). The α-MSH released by POMC neurons then signals to decrease energy intake by binding to melanocortin-4 receptor (MC4R) expressed by MC4R neurons to the paraventricular nucleus (PVN). Conversely, in the 'starved state' activity of agouti-related neuropeptide (AgRP) and of neuropeptide Y (NPY)-expressing neurons is increased by decreased levels of circulating leptin and insulin and by the orexigenic hormone ghrelin to promote food intake. This initial understanding of the melanocortin pathway has recently been implemented by the description of the complex neuronal circuit that controls the activity of POMC, AgRP/NPY and MC4R neurons and downstream signaling by these neurons. This review summarizes the progress done on the melanocortin pathway and describes how...Continue Reading

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Citations

Jul 4, 2020·Current Opinion in Clinical Nutrition and Metabolic Care·Rachel H Freire, Jacqueline I Alvarez-Leite
Jun 17, 2020·The Journal of Clinical Investigation·Xinxia ZhuDaniel L Marks
May 27, 2020·Current Diabetes Reports·Alexandre A da SilvaJohn E Hall
Apr 28, 2019·Current Hypertension Reports·Alexandre A da SilvaJohn E Hall
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Mar 7, 2020·Nutrition Research Reviews·Katy HornerLorraine Brennan
Sep 26, 2020·Journal of Molecular Cell Biology·Yongjie Yang, Yong Xu
Feb 3, 2021·Molecular Metabolism·Henrik H HansenJacob Hecksher-Sørensen
Feb 10, 2021·International Journal of Molecular Sciences·Erica SarchielliMario Maggi
Nov 4, 2020·Molecular and Cellular Pediatrics·Stefanie ZornMartin Wabitsch
Apr 4, 2021·International Journal of Molecular Sciences·P Marcos, R Coveñas
Apr 6, 2021·Open Life Sciences·Kun WangChenguang Du
Apr 26, 2021·Pharmacology & Therapeutics·Reem OdiEmilio Perucca
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