Polymorphisms and mutations in the melanocortin-3 receptor and their relation to human obesity.
Polymorphisms and mutations in the melanocortin-3 receptor and their relation to human obesity.
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DOI：
10.1016/j.bbadis.2017.03.018
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Yanovski JA
中科院分区：
文献类型：
--
作者：
Demidowich AP;Jun JY;Yanovski JA
黑皮质素3受体（Mc3r）的失活突变已被描述为导致小鼠肥胖，但MC3R突变在人类中的生理效应尚不清楚。在这里，我们回顾了在人类中发现的MC 3 R多态性和突变，以及检查其推定影响的体外、小鼠和人类队列研究。一些但不是所有的研究表明，常见的人类MC3R变体T6K+V81I以及其他几种罕见的功能改变突变与更大的肥胖和高瘦素血症以及能量分配改变有关。在体外，T6K+V81I变体似乎降低了MC3R表达，因此降低了响应于配体结合的cAMP生成。敲入小鼠研究证实，T6 K + V81 I变体增加了摄食效率和来源于骨或脂肪组织干细胞的脂肪细胞储存甘油三酯的亲合力。其他MC3R突变在人群中的发生频率太低，无法对其临床效果做出明确的结论。
Inactivating mutations in the melanocortin 3 receptor (Mc3r) have been described as causing obesity in mice, but the physiologic effects of MC3R mutations in humans have been less clear. Here we review the MC3R polymorphisms and mutations identified in humans, and the in vitro, murine, and human cohort studies examining their putative effects. Some, but not all, studies suggest that the common human MC3R variant T6K+V81I, as well as several other rare, function-altering mutations, are associated with greater adiposity and hyperleptinemia with altered energy partitioning. In vitro, the T6K+V81I variant appears to decrease MC3R expression and therefore cAMP generation in response to ligand binding. Knockin mouse studies confirm the T6K+V81I variant increases feeding efficiency and the avidity with which adipocytes derived from bone or adipose tissue stem cells store triglycerides. Other MC3R mutations occur too infrequently in the human population to make definitive conclusions regarding their clinical effects.
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影响因子：
3.5
作者：
Anderson EJ;Çakir I;Carrington SJ;Cone RD;Ghamari-Langroudi M;Gillyard T;Gimenez LE;Litt MJ
通讯作者：
Litt MJ
影响因子：
7.7
作者：
Feng, NP;Young, SF;Yanovski, JA
通讯作者：
Yanovski, JA
影响因子：
4.8
作者：
Begriche, Karima;Levasseur, Peter R.;Butler, Andrew A.
通讯作者：
Butler, Andrew A.
影响因子：
7.3
作者：
Grieco, P;Balse, PM;Hruby, VJ
通讯作者：
Hruby, VJ
影响因子：
5.7
作者：
Boucher, N;Lanouette, CM;Chagnon, YC
通讯作者：
Chagnon, YC