MC3R links nutritional state to childhood growth and the timing of puberty.
MC3R links nutritional state to childhood growth and the timing of puberty.
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DOI：
10.1038/s41586-021-04088-9
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发表时间：
2021-11
期刊：
影响因子：
64.8
通讯作者：
O'Rahilly S
中科院分区：
文献类型：
--
作者：
Lam BYH;Williamson A;Finer S;Day FR;Tadross JA;Gonçalves Soares A;Wade K;Sweeney P;Bedenbaugh MN;Porter DT;Melvin A;Ellacott KLJ;Lippert RN;Buller S;Rosmaninho-Salgado J;Dowsett GKC;Ridley KE;Xu Z;Cimino I;Rimmington D;Rainbow K;Duckett K;Holmqvist S;Khan A;Dai X;Bochukova EG;Genes & Health Research Team;Trembath RC;Martin HC;Coll AP;Rowitch DH;Wareham NJ;van Heel DA;Timpson N;Simerly RB;Ong KK;Cone RD;Langenberg C;Perry JRB;Yeo GS;O'Rahilly S
后生动物身体能量储存的状态被传达给大脑，大脑调节行为、生长、营养分配和发育的关键方面。中枢黑素皮质素系统通过黑素皮质素4受体(MC4R)控制食欲、食物摄入量和能量消耗。在这里，我们提出的证据表明，MC3R调节性成熟的时间、线性增长速度和瘦肉质量的积累，这些都是能量敏感的过程。我们发现，携带MC3R功能丧失突变的人类，包括一个罕见的纯合子个体，青春期的开始时间较晚。与之前在小鼠身上的发现一致，他们还降低了直线生长、瘦身质量和IGF1的循环水平。缺乏Mc3r的小鼠性成熟延迟，生殖周期长度对营养扰动不敏感。Mc3r的表达在控制生殖和生长的下丘脑神经元中丰富，并且在出生后的发育过程中表达增加，这与性成熟的调节性成熟的作用是一致的。这些发现表明，中央黑素皮质素途径是一种营养感知的分叉模型，通过MC4R信号控制卡路里的获取和保留，而通过MC3R信号主要调节卡路里的分配到生长、瘦肉质量和性成熟的时间。
The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1016/j.bbadis.2017.03.018
发表时间：
2017-10
期刊：
Biochimica et biophysica acta. Molecular basis of disease
影响因子：
--
作者：
Demidowich AP;Jun JY;Yanovski JA
通讯作者：
Yanovski JA
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
3
作者：
Chen, AS;Metzger, JM;Van der Ploeg, LHT
通讯作者：
Van der Ploeg, LHT