Role of the melanocortin-4 receptor in metabolic rate and food intake in mice

被引:205
作者
Chen, AS
Metzger, JM
Trumbauer, ME
Guan, XM
Yu, H
Frazier, EG
Marsh, DJ
Forrest, MJ
Gopal-Truter, S
Fisher, J
Camacho, RE
Strack, AM
Mellin, TN
MacIntyre, DE
Chen, HY
Van der Ploeg, LHT [1 ]
机构
[1] Merck Res Labs, Dept Metab Disorders, Rahway, NJ 07065 USA
[2] Merck Res Labs, Dept Anim Pharmacol, Rahway, NJ 07065 USA
[3] Merck Res Labs, Dept Comparat Med, Rahway, NJ 07065 USA
关键词
food intake; melanocortin-4; receptor; metabolic rate; MT-II;
D O I
10.1023/A:1008983615045
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We evaluated the role of the melanocortin-4 receptor (MC-4R) in the control of metabolic rate and food intake in mice. Intraperitoneal administration of the non-selective MC-R agonist melanotan II (MT-II; a cyclic heptapeptide) increases metabolic rate in wildtype mice, while MC-4R knockout mice are insensitive to the effects of MT-II on metabolic rate. MC-4R knockout mice are also insensitive to the effects of MT-II on reducing food intake. We conclude that MC-4R can mediate control of both metabolic rate and food intake in mice. We infer that a role for MC-3R in mediating the acute effects of MT-II on basal metabolic rate and food intake in wildtype mice seems limited.
引用
收藏
页码:145 / 154
页数:10
相关论文
共 35 条
[11]   The mouse mahogany locus encodes a transmembrane form of human attractin [J].
Gunn, TM ;
Miller, KA ;
He, L ;
Hyman, RV ;
Davis, RW ;
Azarani, A ;
Schlossman, SF ;
Duke-Cohan, JS ;
Barsh, GS .
NATURE, 1999, 398 (6723) :152-156
[12]  
Hadley M E, 1998, Pharm Biotechnol, V11, P575
[13]   Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons [J].
Hahn, TM ;
Breininger, JF ;
Baskin, DG ;
Schwartz, MW .
NATURE NEUROSCIENCE, 1998, 1 (04) :271-272
[14]   Receptor-mediated regional sympathetic nerve activation by leptin [J].
Haynes, WG ;
Morgan, DA ;
Walsh, SA ;
Mark, AL ;
Sivitz, WI .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (02) :270-278
[15]   Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic [J].
Haynes, WG ;
Morgan, DA ;
Djalali, A ;
Sivitz, WI ;
Mark, AL .
HYPERTENSION, 1999, 33 (01) :542-547
[16]   Targeted disruption of the melanocortin-4 receptor results in obesity in mice [J].
Huszar, D ;
Lynch, CA ;
FairchildHuntress, V ;
Dunmore, JH ;
Fang, Q ;
Berkemeier, LR ;
Gu, W ;
Kesterson, RA ;
Boston, BA ;
Cone, RD ;
Smith, FJ ;
Campfield, LA ;
Burn, P ;
Lee, F .
CELL, 1997, 88 (01) :131-141
[17]   Interacting appetite-regulating pathways in the hypothalamic regulation of body weight [J].
Kalra, SP ;
Dube, MG ;
Pu, SY ;
Xu, B ;
Horvath, TL ;
Kalra, PS .
ENDOCRINE REVIEWS, 1999, 20 (01) :68-100
[18]   DXA body composition: Theory and practice [J].
Kelly, TL ;
Berger, N ;
Richardson, TL .
APPLIED RADIATION AND ISOTOPES, 1998, 49 (5-6) :511-513
[19]   Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans [J].
Krude, H ;
Biebermann, H ;
Luck, W ;
Horn, R ;
Brabant, G ;
Grüters, A .
NATURE GENETICS, 1998, 19 (02) :155-157
[20]   AGOUTI PROTEIN IS AN ANTAGONIST OF THE MELANOCYTE-STIMULATING-HORMONE RECEPTOR [J].
LU, DS ;
WILLARD, D ;
PATEL, IR ;
KADWELL, S ;
OVERTON, L ;
KOST, T ;
LUTHER, M ;
CHEN, WB ;
WOYCHIK, RP ;
WILKISON, WO ;
CONE, RD .
NATURE, 1994, 371 (6500) :799-802