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Body and mind

Researchers find the gene that makes babies chubby and healthy

The genes that cause babies and other children to gain weight differ from those that make adults overweight. Researchers have now found a genetic reason why babies get chubby cheeks, which is actually a healthy sign.

A major study of 15,000 children in Norway shows that young children who have a very specific but common genetic variant gain weight more easily and get healthy chubby cheeks.

However, this genetic variant does not affect their risk of becoming overweight as adults.

The researchers behind the discovery hope that better understanding of the genetic factors that influence a child’s weight may help to find treatments for children who are not gaining enough weight in early childhood.

The research can also help to determine when children are no longer chubby and healthy but risk a lifelong struggle with obesity.

“We have considerable knowledge about the genetic factors that predispose to obesity among adults, and we also know a lot about the genetic factors that determine birthweight. But we did not know much about the genetic factors that determine what happens between infancy and adulthood. We have come a step closer to understanding this now,” explains one of the researchers behind the new study, Stefan Johansson, Professor and Principal Investigator, Diabetes Research Group, University of Bergen, Norway.

The study, which is a collaboration between Stefan Johansson, Øyvind Helgeland and Pål Rasmus Njølstad from the University of Bergen, has been published in Nature Communications.

Underweight infants risk developing type 2 diabetes as adults

According to Stefan Johansson, discovering more about what causes babies to gain weight is important.

Babies gain substantial weight in relation to their size in their first 3 years of life, but they still need to gain weight at the right rate to prevent them from becoming overweight or underweight.

The body and genes regulate all this.

In addition, children with low birthweight actually have a higher risk of developing obesity and obesity-related diseases such as type 2 diabetes as adults.

“There is considerable debate about this, and some researchers believe that the children end up gaining weight too quickly, which increases the risk of metabolic diseases later in life,” explains Stefan Johansson.

No overlap between chubby 2-year-olds and overweight adults

The new study is based on numerous previous studies that examined the relationship between childhood obesity and the risk of overweight in adulthood.

These studies have shown a massive overlap between children who are overweight at 8 years old and becoming overweight as adults. However, the studies also found no such overlap for children at 2 years old.

“This suggests that preventive measures could be useful when children are overweight at about 5–6 years old. However, we still have to determine what mechanisms take over in the transition from a chubby, healthy toddler to an older child with an increased risk of becoming overweight as an adult. Some evidence suggests that some genes play a role in early childhood but not in adulthood. Something disappears,” explains Stefan Johansson.

Signalling molecules make us feel full

The study indicates that leptin, a signalling molecule, and leptin receptors in the blood and hypothalamus are important in regulating whether we feel hungry or full.

When you eat, leptin is secreted into the blood, and when this reaches the leptin receptors in the hypothalamus, appetite wanes and energy consumption increases.

Some people with rare disorders cannot secrete leptin or lack leptin receptors; they cannot feel full and are constantly hungry instead.

“We can treat children who do not secrete leptin by giving them leptin as medicine. But children who lack the receptors are difficult to treat with medicine, and they often become massively obese and develop obesity-related complications,” says Stefan Johansson.

Leptin receptors in the blood delay feeling full

The researchers examined genetic data from 15,000 children in the Norwegian Mother, Father, and Child Cohort Study, which also has detailed information on the children’s birthweight and 12 weight measurements during their first year of life.

The researchers determined whether specific, common genetic variants affected how much weight the children gained.

The researchers found genetic variants in a gene that causes leptin receptors to be secreted into the blood.

Unlike the leptin receptors in the hypothalamus, which directly control whether a person feels full, Stefan Johansson says that the leptin receptors in the blood may buffer the amount of leptin reaching the brains of young children.

“One possible explanation might be that if there are many leptin receptors in the blood, they bind leptin, slowing the process of reaching the brain. We believe that higher leptin receptor levels in the blood are associated with higher body mass index and thus may buffer against the satiety signal that leptin induces. This may be an important biological mechanism for controlling a child’s rapid growth during the first years of life,” says Stefan Johansson.

Stefan Johansson also says that the researchers will investigate this further and that the Novo Nordisk Foundation has just awarded them a grant to do this.

Finding the chubby child gene

The study revealed that about one quarter of the children had a genetic variant that was already associated at 9 months of age with 300–400 grams of extra fat. This may not sound like much, but Stefan Johansson says that it is quite a lot at that age.

When the researchers sought the same genetic variant among adults, they saw no association between having the genetic variant and being overweight or unhealthy as an adult.

On the contrary, the genetic variant appears to be associated with healthier children.

“This discovery helps us to understand the physiology and genetics of gaining weight in childhood. The leptin receptors are very important, but their effect disappears with age, and other mechanisms take over. The closer we get to understanding when this effect disappears, the better we can determine when it is no longer healthy for a child to have chubby cheeks,” says Stefan Johansson.

Stefan Johansson explains that the study also suggests that genes very strongly determine childhood weight.

“We have found the chubby child gene, which promotes healthy weight gain in early childhood. In the long term, understanding how the gene functions can be used to intervene when children do not gain weight as they should,” says Stefan Johansson.

Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth” has been published in Nature Communications. In 2019, the Novo Nordisk Foundation awarded a grant to Stefan Johansson for the project Infant and Childhood Growth at the Genetic and Molecular Level.

Stefan Johansson
Professor
I have 15 years of experience from genetic studies of both common and rare disorders. My research interests centers around trying to understand the genetic underpinnings of a wide range of disorders such as rare highly heritable genetic disorders, diabetes and related traits and ADHD. I lead the genetics studies in three reserch consortia: KG Jebsen center for Neuropsychiatric Disorders, KG Jebsen Center for Diabetes Research and the Genomics Group at the Dept of Clinical Science and Senter for Medical Genetics and Molecular Medicine.