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

Lam B. Y. H.; Williamson A.; Finer S.; Day F. R.; Tadross J. A.; Goncalves 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.

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

机译：MC3R将营养状态链接到儿童时期的生长和青春期的时机

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The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development(1). The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure(2). 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 delayedsexual maturationand 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.

机译：美唑烷中的躯体能量储存的状态传达给大脑，该大脑调节行为，生长，营养分区和发展的关键方面（1）。中央黑素旋蛋白系统通过Melanocortin 4受体（MC4R）作用，以控制食欲，食物摄入和能量消耗（2）。在这里，我们提出了MC3R调节性成熟的时间，线性生长速率和瘦物质的应激的证据表明，这是全部能敏感过程。我们发现，在MC3R中携带功能丧失的人，包括罕见的Homozygote个体，稍后发作青春期。与小鼠的先前发现一致，它们还具有降低的线性生长，贫质量和IGF1的循环水平。缺乏MC3R的小鼠延迟了对营养扰动的生殖循环长度的不敏感性。 MC3R的表达富集，富含丘脑神经元，其控制繁殖和生长，表达在出生后的发展期间增加，这种方式在性成熟的调节中的作用一致。这些发现表明，通过MC4R通过MC4R进行信号传导，通过MC4R控制卡路里的信号传导的营养感测的分叉模型，而通过MC3R的信令主要调节卡路里的处置成生长，瘦肉质量和性成熟的时机。

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《Nature》 |2021年第7885期|436-441|共6页
作者
Lam B. Y. H.; Williamson A.; Finer S.; Day F. R.; Tadross J. A.; Goncalves 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.;
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作者单位

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England|Univ Cambridge Wellcome MRC Inst Metab Sci MRC Epidemiol Unit Cambridge England;

Queen Mary Univ London Wolfson Inst Populat Hlth Barts & London Sch Med & Dent London England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Epidemiol Unit Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|Univ Cambridge Dept Pathol Cambridge England;

Univ Bristol Bristol Med Sch MRC Integrat Epidemiol Unit & Populat Hlth Sci Bristol Avon England;

Univ Bristol Bristol Med Sch MRC Integrat Epidemiol Unit & Populat Hlth Sci Bristol Avon England;

Univ Michigan Life Sci Inst Ann Arbor MI 48109 USA;

Vanderbilt Univ Sch Med Dept Mol Physiol & Biophys Nashville TN 37212 USA;

Univ Michigan Life Sci Inst Ann Arbor MI 48109 USA;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

Univ Exeter Inst Biomed & Clin Sci Med Sch Exeter Devon England;

German Inst Human Nutr Dept Neurocircuit Dev & Funct Potsdam Germany;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

Ctr Hospitalar & Univ Coimbra Hosp Pediat Med Genet Unit Coimbra Portugal;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

Univ Cambridge Dept Pediat Cambridge England;

Univ Cambridge Dept Pediat Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

NIHR Cambridge Biomed Res Ctr Cambridge England|Univ Cambridge Dept Pediat Cambridge England;

Queen Mary Univ London Wolfson Inst Populat Hlth Barts & London Sch Med & Dent London England;

Queen Mary Univ London Blizard Inst Barts & London Sch Med & Dent London England;

Queen Mary Univ London Blizard Inst Barts & London Sch Med & Dent London England;

Kings Coll London Fac Life Sci & Med Sch Basic & Med Biosci London England;

Wellcome Sanger Inst Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Epidemiol Unit Cambridge England;

Queen Mary Univ London Wolfson Inst Populat Hlth Barts & London Sch Med & Dent London England;

Univ Bristol Bristol Med Sch MRC Integrat Epidemiol Unit & Populat Hlth Sci Bristol Avon England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Epidemiol Unit Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Epidemiol Unit Cambridge England|Charite Univ Med Berlin Berlin Inst Hlth Computat Med Berlin Germany;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Epidemiol Unit Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

Univ Cambridge Wellcome MRC Inst Metab Sci MRC Metab Dis Unit Cambridge England|NIHR Cambridge Biomed Res Ctr Cambridge England;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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1. Childhood diet and growth in boys in relation to timing of puberty and adult height: the Longitudinal Studies of Child Health and Development [J] . Alimujiang Aliya, Colditz Graham A., Gardner Jane D., Cancer causes and control: CCC . 2018,第10期

机译：与青春期和成人高度的时期的儿童饮食和生长：儿童健康和发展的纵向研究
2. Childhood diet and growth in boys in relation to timing of puberty and adult height: the Longitudinal Studies of Child Health and Development [J] . Alimujiang Aliya, Colditz Graham A., Gardner Jane D., Cancer causes and control: CCC . 2018,第10期

机译：儿童饮食与男孩的成长与青春期和成人高度的时间相关：儿童健康和发展的纵向研究
3. Diet Quality in Childhood Is Prospectively Associated with the Timing of Puberty but Not with Body Composition at Puberty Onset [J] . Guo Cheng, Steffi Gerlach, Lars Libuda, Journal of Nutrition . 2010,第1期

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4. Can Differing Pre- and Post-Weaning Phase Nutrition Change Intake, Growth and Hasten Puberty in Holstein Heifer Calves? [C] . Animal Nutrition Conference of Canada . 2018

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5. Early Puberty: Adulthood Metabolic Consequences and Childhood Nutritional Determinants. [D] . Mueller, Noel Theodore. 2013

机译：青春期早期：成年后的代谢后果和儿童的营养决定因素。
6. Childhood Diet And Growth In Boys In Relation To Timing Of Puberty And Adult Height: The Longitudinal Studies Of Child Health And Development [O] . Aliya Alimujiang, Graham A. Colditz, Jane D. Gardner, -1

机译：男孩的饮食和成长与青春期和成人身高的时间关系：儿童健康与发育的纵向研究
7. Childhood diet and growth in boys in relation to timing of puberty and adult height: the Longitudinal Studies of Child Health and Development [O] . Aliya Alimujiang, Graham A. Colditz, Jane D. Gardner, 2018

机译：儿童饮食与男孩的成长与青春期和成人高度的时间相关：儿童健康和发展的纵向研究

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

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