The role of melanocortins in body weight regulation: opportunities for the treatment of obesity.
Five G-protein-coupled melanocortin receptors (MC(1)-MC(5)) are expressed in mammalian tissues. The melanocortin receptors support diverse physiological functions, including the regulation of hair color, adrenal function, energy homeostasis, feed efficiency, sebaceous gland lipid production and immune and sexual function. The melanocortins (adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), beta-MSH and gamma-MSH) are agonist peptide ligands for the melanocortin receptors and these peptides are processed from the pre-prohormone proopiomelanocortin (POMC). Peptide antagonists for the melanocortin MC(1), MC(3) and MC(4) receptors include agouti-related protein (AgRP) and agouti. Diverse lines of evidence, including genetic and pharmacological data obtained in rodents and humans, support a role for the melanocortin MC(3) and MC(4) receptors in the regulation of energy homeostasis. Recent advances in the development of potent and selective peptide and non-peptide melanocortin receptor ligands are anticipated to help unravel the roles for the melanocortin receptors in humans and to accelerate the clinical use of small molecule melanocortin mimetics.
MacNeil
Douglas J
DJ
Merck Research Laboratories, Rahway, NJ 07065, USA.
Howard
Andrew D
AD
Guan
Xiaoming
X
Fong
Tung M
TM
Nargund
Ravi P
RP
Bednarek
Maria A
MA
Goulet
Mark T
MT
Weinberg
David H
DH
Strack
Alison M
AM
Marsh
Donald J
DJ
Chen
Howard Y
HY
Shen
Chun-Pyn
CP
Chen
Airu S
AS
Rosenblum
Charles I
CI
MacNeil
Tanya
T
Tota
Michael
M
MacIntyre
Euan D
ED
Van der Ploeg
Lex H T
LH
D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology*; D018043:Receptors, Corticotropin / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D044101:Receptors, Melanocortin
D019440:Anti-Obesity Agents; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D009074:Melanocyte-Stimulating Hormones