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MC3R links nutritional state to childhood growth and the timing of puberty
- Source :
- Nature, 2021, ' MC3R links nutritional state to childhood growth and the timing of puberty ', Nature, vol. 599, no. 7885, pp. 436-441 . https://doi.org/10.1038/s41586-021-04088-9
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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. MC3R deficiency is associated with a delay in the onset of puberty, and a reduction in growth and lean mass.
- Subjects :
- Male
medicine.medical_specialty
Time Factors
Calorie
Adolescent
media_common.quotation_subject
Hypothalamus
Nutritional Status
Estrous Cycle
Nutrient sensing
Biology
Weight Gain
Article
Mice
Child Development
Central melanocortin system
Internal medicine
medicine
Animals
Humans
Sexual maturity
Obesity
Sexual Maturation
Insulin-Like Growth Factor I
Child
media_common
Aged, 80 and over
Menarche
Multidisciplinary
Homozygote
Puberty
Appetite
Melanocortins
Melanocortin 4 receptor
Phenotype
medicine.anatomical_structure
Endocrinology
Lean body mass
Female
Melanocortin
Receptor, Melanocortin, Type 3
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 599
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....2690bb58b6dc1e9ea01491ecfdde0e49