The role of melanocortins in body weight regulation: opportunities for the treatment of obesity

被引:62
作者
MacNeil, DJ [1 ]
Howard, AD [1 ]
Guan, XM [1 ]
Fong, TM [1 ]
Nargund, RP [1 ]
Bednarek, MA [1 ]
Goulet, MT [1 ]
Weinberg, DH [1 ]
Strack, AM [1 ]
Marsh, DJ [1 ]
Chen, HY [1 ]
Shen, CP [1 ]
Chen, ARS [1 ]
Rosenblum, CI [1 ]
MacNeil, T [1 ]
Tota, M [1 ]
MacIntyre, ED [1 ]
Van der Ploeg, LHT [1 ]
机构
[1] Merck Res Labs, Rahway, NJ 07065 USA
关键词
melanocortins; melanocortin receptor; neuropeptide; ACTH (adrenocorticotropic hormone); AgRP (agouti-related protein); POMC (proopiomelanocortin); energy homeostasis; obesity; sexual function;
D O I
10.1016/S0014-2999(02)01425-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Five G-protein-coupled melanocortin receptors (MC1-MC5) 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 MC1, MC3 and MC4 receptors include agoutirelated protein (AgRP) and agouti. Diverse lines of evidence, including genetic and pharmacological data obtained in rodents and humans, support a role for the melanocortin MC3 and MC4 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. (C) 2002 Elsevier Science B.V All rights reserved.
引用
收藏
页码:141 / 157
页数:17
相关论文
共 153 条
[51]   Role of melanocortinergic neurons in feeding and the agouti obesity syndrome [J].
Fan, W ;
Boston, BA ;
Kesterson, RA ;
Hruby, VJ ;
Cone, RD .
NATURE, 1997, 385 (6612) :165-168
[52]   Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency [J].
Farooqi, IS ;
Yeo, GSH ;
Keogh, JM ;
Aminian, S ;
Jebb, SA ;
Butler, G ;
Cheetham, T ;
O'Rahilly, S .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 106 (02) :271-279
[53]   CLONING, EXPRESSION, AND TISSUE DISTRIBUTION OF A 5TH MELANOCORTIN RECEPTOR SUBTYPE [J].
FATHI, Z ;
IBEN, LG ;
PARKER, EM .
NEUROCHEMICAL RESEARCH, 1995, 20 (01) :107-113
[54]   ART (protein product of agouti-related transcript) as an antagonist of MC-3 and MC-4 receptors [J].
Fong, TM ;
Mao, C ;
MacNeil, T ;
Kalyani, R ;
Smith, T ;
Weinberg, D ;
Tota, MR ;
VanderPloeg, LHT .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 237 (03) :629-631
[55]   A melanocortin agonist reduces neuronal firing rate in rat hypothalamic slices [J].
Fong, TM ;
Van der Ploeg, LHT .
NEUROSCIENCE LETTERS, 2000, 283 (01) :5-8
[56]   NPY Y1 receptor like immunoreactivity exists in a subpopulation of beta-endorphin immunoreactive nerve cells in the arcuate nucleus: A double immunolabelling analysis in the rat [J].
Fuxe, K ;
Tinner, B ;
Caberlotto, L ;
Bunnemann, B ;
Agnati, LF .
NEUROSCIENCE LETTERS, 1997, 225 (01) :49-52
[57]  
GANTZ I, 1993, J BIOL CHEM, V268, P8246
[58]  
GIULIANO FA, 1995, UROL CLIN N AM, V22, P747
[59]   Oral sildenafil in the treatment of erectile dysfunction [J].
Goldstein, I ;
Lue, TF ;
Padma-Nathan, H ;
Rosen, RC ;
Steers, WD ;
Wicker, PA .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 338 (20) :1397-1404
[60]   MOLECULAR-CLONING AND CHARACTERIZATION OF THE RAT 5TH MELANOCORTIN RECEPTOR [J].
GRIFFON, N ;
MIGNON, V ;
FACCHINETTI, P ;
DIAZ, J ;
SCHWARTZ, JC ;
SOKOLOFF, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 200 (02) :1007-1014