Regulation of feeding and energy homeostasis by α-MSH
- Erica J. P. Anderson,
- Isin Cakir,
- Sheridan Carrington,
- Roger Cone⇑,
- Masoud Ghamari-Langroudi,
- Taneisha Gillyard,
- Luis E Gimenez and
- Michael Litt
- E Anderson, Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States
- I Cakir, Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States
- S Carrington, Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States
- R Cone, Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States
- M Ghamari-Langroudi, Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States
- T Gillyard, Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States
- L Gimenez, Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States
- M Litt, Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States
- Correspondence: Roger Cone, Email: roger.cone{at}vanderbilt.edu
Abstract
The melanocortin peptides derived from proopiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte stimulating hormone (α-MSH) on pigmentation and adrenocorticotropic hormone (ACTH) 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 central nervous system, 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.
- Received 22 January 2016
- Revision received 22 February 2016
- Accepted 1 March 2016
- Accepted Preprint first posted online on 3 March 2016
