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The connection between puberty, body mass, and nutrition

This study used genome sequencing methods to find links between mutations in the gene for the melanocortin 3 hormone, delayed puberty, and high body mass. This hormone tells the body when to enter puberty and how to grow.

Image Credit: By Sciworthy

If you have ever had a younger sibling or child that you have watched grow up, you know that there are a lot of changes that humans go through from infancy to adulthood. To an extent, our development is controlled by how we eat, move, and think. We know that the genes we get from our parents play a role, too. However, we don’t know much about how these two things interact.

Genes are the blueprints of all living things. They are made of a DNA code that tells the different cells in our bodies how to operate, what proteins to produce, and when to function. Genes affect many aspects about us, such as our eye color and how many limbs we have. However, they do not have the final say in our development. For example, if a growing child does not get enough food, their genes will cause them to go into puberty later and affect their height, weight, and other traits. A research study was done by scientists in the UK, Germany, Portugal, and the USA to better understand how our nutrition and genes work together to direct development.

Researchers have known about a group of genes that control how we respond to food. These are called the melanocortin receptors. Signals from our bodies tell our melanocortin receptors how much food we are eating so they can control our behavior and response. One type, the melanocortin 4 receptor, tells our brains whether we are hungry or not and how much energy to burn from the food we eat. People without this gene feel hungry all the time but do not burn a lot of energy, leading to problems with obesity.

There is more than one kind of melanocortin receptor. Most of what we know about these receptors comes from studies on melanocortin 4, which is in our brains. When the researchers looked for other melanocortin receptors in the brain, they found melanocortin 3. Not much was known about this receptor, so the scientists decided to study human patients with defects in this gene.

The scientists first studied the melanocortin 3 receptors of 200,000 UK residents and found that 0.82% of them had a defect in this gene. These defects damaged the gene, making it less effective. Of the 1,640 people with defective melanocortin 3 receptors, almost all of them entered puberty several months later than normal.

The researchers then studied the DNA code of this gene and used computational tools to predict what a broken melanocortin 3 receptor would look like. With this, 6 participants were found with a single copy of the broken gene, either from their mother or their father. These participants were much shorter, had a lower lean body mass, and weighed less than the average.

They hypothesized that two broken copies of the gene would have even stronger effects. After searching through many data sets from around the world, a single person with two broken copies was found. This person started puberty extremely late, in their 20’s. They were very short and had a low lean body mass. However, unlike those with only one broken copy of the gene, they had a higher than average body fat percentage.

While the human data told the scientists a lot about the melanocortin 3 receptor, it all came from adults who were past puberty. To study how this gene affects different aspects of puberty, the researchers studied mice with two broken copies of the melanocortin 3 receptor. These mice, like the human participants, experienced delayed puberty. Additionally, female mice had longer oestrous cycles, the mouse equivalent of the human menstrual cycle.

While hormonal cycles are often delayed when we don’t get enough food, the oestrous cycles of mice with broken copies of the melanocortin 3 receptor were no different than normal mice. When the brains of normal mice and broken-gene mice were compared, the scientists found that a lot of melanocortin 3 receptors were expressed in brain cells that control hormones.

These findings  suggest that the melanocortin 3 receptor is critical for connecting our nutrition to our development. The scientists suggest that this receptor is included in future genetic testing but point out that more human patients are needed in order to confirm how this gene works.

Study Information

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

Study was published on: 11/03/2021

Study author(s): 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. Buller, J. Rosmaninho-Salgado, G. K. C. Dowsett, K. E. Ridley, Z. Xu, I. Cimino, D. Rimmington, K. Rainbow, K. Duckett, S. Holmqvist, A. Khan, X. Dai, E. G. Bochukova, Genes & Health Research Team, R. C. Trembath, H. C. Martin, A. P. Coll, D. H. Rowitch, N. J. Wareham, D. A. van Heel, N. Timpson, R. B. Simerly, K. K. Ong, R. D. Cone, C. Langenberg, J. R. B. Perry, G. S. Yeo & S. O’Rahilly

The study was done at: University of Cambridge (UK), NIHR Cambridge Biomedical Research Center (UK), Queen Mary University (UK), University of Bristol (UK), University of Michigan (USA), Vanderbilt University (USA), University of Exeter Medical School (UK), German Institute of Human Nutrition (Germany), Centro Hospitalar e Universitário de Coimbra (Portugal), King's College London (UK), Wellcome Sanger Institute (UK), Berlin Institute of Health (Germany)

The study was funded by: UK Medical Research Council, Wellcome Trust, National Institute for Health Research, Biotechnology and Biological Sciences Research Council (BBSRC), University of Cambridge, AstraZeneca, Cancer Research UK, Elizabeth Blackwell Institute for Health Research, University of Bristol ALSPAC, Higher Education Funding Council for England Catalyst, Barts Charity, Health Data Research, Diabetes Research and Wellness Foundation, US National Institutes of Health (NIH)

Raw data availability: Not available

Featured image credit: By Sciworthy

This summary was edited by: Gina Misra