IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v599y2021i7885d10.1038_s41586-021-04088-9.html
   My bibliography  Save this article

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

Author

Listed:
  • B. Y. H. Lam

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • A. Williamson

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre
    MRC Epidemiology Unit, Wellcome–MRC Institute of Metabolic Science, University of Cambridge)

  • S. Finer

    (Wolfson Institute of Population Health, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • F. R. Day

    (MRC Epidemiology Unit, Wellcome–MRC Institute of Metabolic Science, University of Cambridge)

  • J. A. Tadross

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre
    University of Cambridge)

  • A. Gonçalves Soares

    (University of Bristol)

  • K. Wade

    (University of Bristol)

  • P. Sweeney

    (University of Michigan)

  • M. N. Bedenbaugh

    (Vanderbilt University)

  • D. T. Porter

    (University of Michigan)

  • A. Melvin

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • K. L. J. Ellacott

    (University of Exeter Medical School)

  • R. N. Lippert

    (German Institute of Human Nutrition)

  • S. Buller

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • J. Rosmaninho-Salgado

    (Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra)

  • G. K. C. Dowsett

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • K. E. Ridley

    (University of Cambridge)

  • Z. Xu

    (University of Cambridge)

  • I. Cimino

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • D. Rimmington

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • K. Rainbow

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • K. Duckett

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • S. Holmqvist

    (University of Cambridge)

  • A. Khan

    (Wolfson Institute of Population Health, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • X. Dai

    (Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London)

  • E. G. Bochukova

    (Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London)

  • R. C. Trembath

    (King’s College London)

  • H. C. Martin

    (Wellcome Sanger Institute, Hinxton)

  • A. P. Coll

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • D. H. Rowitch

    (University of Cambridge)

  • N. J. Wareham

    (MRC Epidemiology Unit, Wellcome–MRC Institute of Metabolic Science, University of Cambridge)

  • D. A. van Heel

    (Wolfson Institute of Population Health, Barts and the London School of Medicine and Dentistry, Queen Mary University of London
    Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London)

  • N. Timpson

    (University of Bristol)

  • R. B. Simerly

    (Vanderbilt University)

  • K. K. Ong

    (MRC Epidemiology Unit, Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    University of Cambridge)

  • R. D. Cone

    (University of Michigan
    University of Michigan)

  • C. Langenberg

    (MRC Epidemiology Unit, Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    Berlin Institute of Health at Charité–Universitätsmedizin Berlin)

  • J. R. B. Perry

    (MRC Epidemiology Unit, Wellcome–MRC Institute of Metabolic Science, University of Cambridge)

  • G. S. Yeo

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • S. O’Rahilly

    (Wellcome–MRC Institute of Metabolic Science, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

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.

Suggested Citation

  • B. Y. H. Lam & A. Williamson & S. Finer & F. R. Day & J. A. Tadross & A. Gonçalves Soares & K. Wade & P. Sweeney & M. N. Bedenbaugh & D. T. Porter & A. Melvin & K. L. J. Ellacott & R. N. Lippert & S. , 2021. "MC3R links nutritional state to childhood growth and the timing of puberty," Nature, Nature, vol. 599(7885), pages 436-441, November.
  • Handle: RePEc:nat:nature:v:599:y:2021:i:7885:d:10.1038_s41586-021-04088-9
    DOI: 10.1038/s41586-021-04088-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-04088-9
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-021-04088-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Aurino, Elisabetta & Lleras-Muney, Adriana & Tarozzi, Alessandro & Tinoco, Brendan, 2023. "The rise and fall of SES gradients in heights around the world," Journal of Health Economics, Elsevier, vol. 91(C).

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:599:y:2021:i:7885:d:10.1038_s41586-021-04088-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.