MC3R relates nutritional status to timing of child growth and puberty

Lam, BYH, Williamson, A., Finer, S., etal. MC3R relates nutritional status to timing of child growth and puberty. Nature (2021). https://doi.org/10.1038/s41586-021-04088-9

Commentary

The state of somatic energy storage in the metazoan is communicated to the brain, which regulates critical aspects of behavior, growth, nutrient distribution and development.

The central melanocortin system acts via the melanocortin 4 receptor (MC4R) to regulate appetite, food intake, and energy expenditure. In this study, we present evidence that the MC3R regulates the timing of sexual maturation, the rate of linear growth, and the development of lean body mass.

Humans with loss-of-function mutations in the MC3R, including rare homozygous individuals, were found to develop puberty later, and consistent with findings in mice, they were observed to have reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and insensitivity of the length of the reproductive cycle to nutritional perturbations.

Mc3r expression is enriched in hypothalamic neurons that control reproduction and growth, and its expression increases during postnatal development in a manner consistent with its role in regulating sexual maturation. These findings suggest a divergent model of nutrient sensing by the central melanocortin pathway in which MC4R-mediated signaling regulates caloric acquisition and retention, whereas MC3R-mediated signaling primarily regulates caloric growth, lean mass, and transition to the timing of sexual maturation.