小柯机器人

英国剑桥大学S. O’Rahilly研究团队发现，MC3R连接营养状态与幼年成长和青春期时间。相关论文于2021年11月3日在线发表在《自然》杂志上。

据研究人员介绍，后生动物中体细胞能量储存的状态被传达到大脑，大脑调节行为、生长、营养分配和发育的关键方面。中枢黑皮质素系统通过黑皮质素4受体（MC4R）来控制食欲、食物摄入和能量消耗。

研究人员提供的证据表明MC3R调节性成熟的时间、线性增长的速度和瘦体重的增加，这些都是能量敏感的过程。研究人员发现携带MC3R功能丧失突变的人类，包括罕见的纯合个体，青春期开始较晚。与之前在小鼠中的发现一致，它们的线性生长、瘦体重和IGF1循环水平也有所降低。缺乏Mc3r的小鼠性成熟延迟，生殖周期长度对营养干扰不敏感。

Mc3r的表达在控制生殖和生长的下丘脑神经元中富集，并且在出生后发育过程中表达增加，其方式与性成熟调节中的作用一致。这些发现表明中枢黑皮质素通路的营养感知分叉模型，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在生长、瘦体重和性成熟时间中的分配。 

附：英文原文

Title: MC3R links nutritional state to childhood growth and the timing of puberty

Author: Lam, B. Y. H., Williamson, A., Finer, S., Day, F. R., Tadross, J. A., Gonalves Soares, A., Wade, K., Sweeney, P., Bedenbaugh, M. N., Porter, D. T., Melvin, A., Ellacott, K. L. J., Lippert, R. N., Buller, S., Rosmaninho-Salgado, J., Dowsett, G. K. C., Ridley, K. E., Xu, Z., Cimino, I., Rimmington, D., Rainbow, K., Duckett, K., Holmqvist, S., Khan, A., Dai, X., Bochukova, E. G., Trembath, R. C., Martin, H. C., Coll, A. P., Rowitch, D. H., Wareham, N. J., van Heel, D. A., Timpson, N., Simerly, R. B., Ong, K. K., Cone, R. D., Langenberg, C., Perry, J. R. B., Yeo, G. S., ORahilly, S.

Issue&Volume: 2021-11-03

Abstract: The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. 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.

DOI: 10.1038/s41586-021-04088-9

Source: https://www.nature.com/articles/s41586-021-04088-9

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