Loss of Function of the Melanocortin 2 Receptor Accessory Protein 2 Is Associated with Mammalian Obesity

被引：220

作者：

Asai, Masato ^{[1
,2
,3
,4
]}

Ramachandrappa, Shwetha ^{[5
,6
]}

Joachim, Maria ^{[1
]}

Shen, Yuan ^{[1
]}

Zhang, Rong ^{[1
]}

Nuthalapati, Nikhil ^{[1
]}

Ramanathan, Visali ^{[1
]}

Strochlic, David E. ^{[1
]}

Ferket, Peter ^{[7
]}

Linhart, Kirsten ^{[1
]}

Ho, Caroline ^{[1
]}

Novoselova, Tatiana V. ^{[8
]}

Garg, Sumedha ^{[5
,6
]}

Ridderstrale, Martin ^{[9
,10
]}

Marcus, Claude ^{[11
]}

Hirschhorn, Joel N. ^{[1
,12
,13
]}

Keogh, Julia M. ^{[5
,6
]}

O'Rahilly, Stephen ^{[5
,6
]}

Chan, Li F. ^{[8
]}

Clark, Adrian J. ^{[8
]}

Farooqi, I. Sadaf ^{[5
,6
]}

Majzoub, Joseph A. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Endocrinol,Dept Med, Boston, MA 02115 USA

[2] Nagoya Univ, Grad Sch Med, Dept Pathol, Showa Ku, Nagoya, Aichi 4668550, Japan

[3] Nagoya Univ, Grad Sch Med, Dept Endocrinol, Showa Ku, Nagoya, Aichi 4668550, Japan

[4] Nagoya Univ, Grad Sch Med, Dept Diabet, Showa Ku, Nagoya, Aichi 4668550, Japan

[5] Univ Cambridge, Metab Res Labs, Cambridge CB2 0QQ, England

[6] Addenbrookes Hosp, Inst Metab Sci, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England

[7] N Carolina State Univ, Prestage Dept Poultry Sci, Raleigh, NC 27695 USA

[8] Univ London, Barts & London Sch Med & Dent, Ctr Endocrinol, William Harvey Res Inst, London EC1M 6BQ, England

[9] Lund Univ, Dept Clin Sci, Malmo, Sweden

[10] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[11] Karolinska Inst, Natl Childhood Obes Ctr, Dept Clin Sci Intervent & Technol, Div Pediat, S-14186 Huddinge, Sweden

[12] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02142 USA

[13] Broad Inst, Cambridge, MA 02142 USA

来源：

SCIENCE | 2013年 / 341卷 / 6143期

基金：

英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

MRAP2;

D O I：

10.1126/science.1233000

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin receptors in vitro. To investigate the physiological role of brain-expressed melanocortin 2 receptor accessory protein 2 (MRAP2), we characterized mice with whole-body and brain-specific targeted deletion of Mrap2, both of which develop severe obesity at a young age. Mrap2 interacts directly with melanocortin 4 receptor (Mc4r), a protein previously implicated in mammalian obesity, and it enhances Mc4r-mediated generation of the second messenger cyclic adenosine monophosphate, suggesting that alterations in Mc4r signaling may be one mechanism underlying the association between Mrap2 disruption and obesity. In a study of humans with severe, early-onset obesity, we found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans.

引用

页码：275 / 278

页数：4

共 13 条

[1]

Divergence of melanocortin pathways in the control of food intake and energy expenditure [J].