title: 60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH.
abstract: The melanocortin peptides derived from pro-opiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte-stimulating hormone (α-MSH) on pigmentation and adrenocorticotrophic hormone on adrenocortical glucocorticoid production. However, the discovery of POMC mRNA and melanocortin peptides in the CNS generated activities directed at understanding the direct biological actions of melanocortins in the brain. Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the development of pharmacological tools and genetic models leading to the demonstration that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Indeed, mutations in MC4R are now known to be the most common cause of early onset syndromic obesity, accounting for 2-5% of all cases. This review discusses the history of these discoveries, as well as the latest work attempting to understand the molecular and cellular basis of regulation of feeding and energy homeostasis by the predominant melanocortin peptide in the CNS, α-MSH.
authors.affiliation: Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Erica J P
authors.initials: EJ
authors.lastname: Anderson
authors.affiliation: Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Isin
authors.initials: I
authors.lastname: Çakir
authors.affiliation: Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Sheridan J
authors.initials: SJ
authors.lastname: Carrington
authors.affiliation: Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA roger.cone@vanderbilt.edu.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cone
authors.affiliation: Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Masoud
authors.initials: M
authors.lastname: Ghamari-Langroudi
authors.affiliation: Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA Meharry Medical CollegeDepartment of Neuroscience and Pharmacology, Nashville, Tennessee, USA.
authors.forename: Taneisha
authors.initials: T
authors.lastname: Gillyard
authors.affiliation: Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Gimenez
authors.affiliation: Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Litt
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D003001:Cloning, Molecular; D004734:Energy Metabolism / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D062308:Optogenetics / Q000379:methods; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D020033:Protein Isoforms; D044101:Receptors, Melanocortin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000521:alpha-MSH / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D054369:Agouti-Related Protein; C458099:MRAP protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms; D044101:Receptors, Melanocortin; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin
keywords: MC4R; POMC; food intake; melanocortin; α-MSH