This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coll, A. P. Articles by O’Rahilly, S. Search for Related Content PubMed PubMed Citation Articles by Coll, A. P. Articles by O’Rahilly, S.

Proopiomelanocortin and Energy Balance: Insights from Human and Murine Genetics

University Departments of Medicine and Clinical Biochemistry, Cambridge Institute of Medical Research, Addenbrooke’s Hospital, Cambridge, United Kingdom CB2 2QQ

Address all correspondence and requests for reprints to: Dr. Stephen O’Rahilly, University Departments of Medicine and Clinical Biochemistry, Box 232, Addenbrooke’s Hospital, Cambridge, United Kingdom CB2 2QR. E-mail: sorahill{at}hgmp.mrc.ac.uk.

Proopiomelanocortin (POMC) undergoes extensive and tissuespecific posttranslational processing to yield a range of biologically active peptides. Historically, the most clearly defined roles of these peptides are in the control of adrenal steroidogenesis by corticotroph-derived ACTH and skin pigmentation by MSH. However, a rapidly expanding body of work has established that POMC-derived peptides synthesized in neurons of the hypothalamus play a central role in the control of energy homeostasis. We review how inherited abnormalities in POMC synthesis and processing and defects in the action of POMC-derived peptides in both humans and mice have helped shape our current understanding of the importance of the melanocortin system in human energy balance.

This work was supported by the Wellcome Trust, the United Kingdom Medical Research Council, and a Raymond and Beverly Sackler Fellowship (to A.P.C.).

Abbreviations: AGRP, Agouti-related protein; GLP-2, glucagon-like peptide-2; MC3R, melanocortin receptor type 3; PC, prohormone convertase; POMC, proopiomelanocortin; WT, wild type.

This article has been cited by other articles:

				D. Tsao, H. K. Thomsen, J. Chou, J. Stratton, M. Hagen, C. Loo, C. Garcia, D. L. Sloane, A. Rosenthal, and J. C. Lin TrkB Agonists Ameliorate Obesity and Associated Metabolic Conditions in Mice Endocrinology, March 1, 2008; 149(3): 1038 - 1048. [Abstract] [Full Text] [PDF]

				E. A. Nillni Regulation of Prohormone Convertases in Hypothalamic Neurons: Implications for ProThyrotropin-Releasing Hormone and Proopiomelanocortin Endocrinology, September 1, 2007; 148(9): 4191 - 4200. [Abstract] [Full Text] [PDF]

				J. Miyamoto, T. Matsumoto, H. Shiina, K. Inoue, I. Takada, S. Ito, J. Itoh, T. Minematsu, T. Sato, T. Yanase, et al. The Pituitary Function of Androgen Receptor Constitutes a Glucocorticoid Production Circuit Mol. Cell. Biol., July 1, 2007; 27(13): 4807 - 4814. [Abstract] [Full Text] [PDF]

				M. Lee, A. Kim, S. C. Chua Jr., S. Obici, and S. L. Wardlaw Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E121 - E131. [Abstract] [Full Text] [PDF]

				M. Perello, R. C. Stuart, and E. A. Nillni Differential effects of fasting and leptin on proopiomelanocortin peptides in the arcuate nucleus and in the nucleus of the solitary tract Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1348 - E1357. [Abstract] [Full Text] [PDF]

				H. Shimizu, K. Inoue, and M. Mori The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure J. Endocrinol., April 1, 2007; 193(1): 1 - 9. [Abstract] [Full Text] [PDF]

				J. L. Smart, V. Tolle, V. Otero-Corchon, and M. J. Low Central Dysregulation of the Hypothalamic-Pituitary-Adrenal Axis in Neuron-Specific Proopiomelanocortin-Deficient Mice Endocrinology, February 1, 2007; 148(2): 647 - 659. [Abstract] [Full Text] [PDF]

				Y. C. L. Tung, S. J. Piper, D. Yeung, S. O'Rahilly, and A. P. Coll A Comparative Study of the Central Effects of Specific Proopiomelancortin (POMC)-Derived Melanocortin Peptides on Food Intake and Body Weight in Pomc Null Mice Endocrinology, December 1, 2006; 147(12): 5940 - 5947. [Abstract] [Full Text] [PDF]

				T. M. Williams and K. B. Donnelly Gastric Mucosal Damage Following Repeat Administration of Melanocortin Subtype-4 Receptor Ligands to Fischer 344 Rats Toxicol Pathol, October 1, 2006; 34(6): 738 - 743. [Abstract] [PDF]

				I. S. Farooqi, S. Drop, A. Clements, J. M. Keogh, J. Biernacka, S. Lowenbein, B. G. Challis, and S. O'Rahilly Heterozygosity for a POMC-Null Mutation and Increased Obesity Risk in Humans Diabetes, September 1, 2006; 55(9): 2549 - 2553. [Abstract] [Full Text] [PDF]

				A. P Coll, M. Fassnacht, S. Klammer, S. Hahner, D. M Schulte, S. Piper, Y C L. Tung, B. G Challis, Y. Weinstein, B. Allolio, et al. Peripheral administration of the N-terminal pro-opiomelanocortin fragment 1-28 to Pomc-/- mice reduces food intake and weight but does not affect adrenal growth or corticosterone production. J. Endocrinol., August 1, 2006; 190(2): 515 - 525. [Abstract] [Full Text] [PDF]

				G. M. Sutton, J. L. Trevaskis, M. W. Hulver, R. P. McMillan, N. J. Markward, M. J. Babin, E. A. Meyer, and A. A. Butler Diet-Genotype Interactions in the Development of the Obese, Insulin-Resistant Phenotype of C57BL/6J Mice Lacking Melanocortin-3 or -4 Receptors Endocrinology, May 1, 2006; 147(5): 2183 - 2196. [Abstract] [Full Text] [PDF]

				F. H. Koegler, P. J. Enriori, S. K. Billes, D. L. Takahashi, M. S. Martin, R. L. Clark, A. E. Evans, K. L. Grove, J. L. Cameron, and M. A. Cowley Peptide YY(3-36) Inhibits Morning, but Not Evening, Food Intake and Decreases Body Weight in Rhesus Macaques Diabetes, November 1, 2005; 54(11): 3198 - 3204. [Abstract] [Full Text] [PDF]

				M. Baker, N. Gaukrodger, B. M. Mayosi, H. Imrie, M. Farrall, H. Watkins, J. M.C. Connell, P. J. Avery, and B. Keavney Association Between Common Polymorphisms of the Proopiomelanocortin Gene and Body Fat Distribution: A Family Study Diabetes, August 1, 2005; 54(8): 2492 - 2496. [Abstract] [Full Text] [PDF]

				P. Buono, F. Pasanisi, C. Nardelli, L. Ieno, S. Capone, R. Liguori, C. Finelli, G. Oriani, F. Contaldo, and L. Sacchetti Six Novel Mutations in the Proopiomelanocortin and Melanocortin Receptor 4 Genes in Severely Obese Adults Living in Southern Italy Clin. Chem., August 1, 2005; 51(8): 1358 - 1364. [Abstract] [Full Text] [PDF]

				F. S. J. de Souza, A. M. Santangelo, V. Bumaschny, M. E. Avale, J. L. Smart, M. J. Low, and M. Rubinstein Identification of Neuronal Enhancers of the Proopiomelanocortin Gene by Transgenic Mouse Analysis and Phylogenetic Footprinting Mol. Cell. Biol., April 15, 2005; 25(8): 3076 - 3086. [Abstract] [Full Text] [PDF]

				S. M. Appleyard, T. W. Bailey, M. W. Doyle, Y.-H. Jin, J. L. Smart, M. J. Low, and M. C. Andresen Proopiomelanocortin Neurons in Nucleus Tractus Solitarius Are Activated by Visceral Afferents: Regulation by Cholecystokinin and Opioids J. Neurosci., April 6, 2005; 25(14): 3578 - 3585. [Abstract] [Full Text] [PDF]

				ABDOMINAL OBESITY STUDY GROUP, F. E. VON EYBEN, J. P. KROUSTRUP, J. F. LARSEN, and J. CELIS Comparison of Gene Expression in Intra-Abdominal and Subcutaneous Fat: A Study of Men with Morbid Obesity and Nonobese Men Using Microarray and Proteomics Ann. N.Y. Acad. Sci., December 1, 2004; 1030(1): 508 - 536. [Abstract] [Full Text] [PDF]