Obesity Starts in the Developing Brain: Study

Marcia Frellick

October 06, 2022

What if a baby's developing brain at the critical time just before birth and in the early days after establish the lifetime risk for obesity?

Previous research has suggested that human genes associated with obesity determine whether a person will have a hard time maintaining a healthy weight later in life. For decades, researchers have looked for links between genetic variants and body mass index (BMI), explains Robert Waterland, PhD, professor of pediatrics-nutrition at Baylor College of Medicine in Houston, Texas. The problem, he says, is the genetic ties found so far don't explain weight gain and who is most at risk.

Could there be more behind rising obesity rates than genetics and lifestyle?

In their new study published in Science Advances, Waterland and his team looked at the possibility that environmental influences – such as poor nutrition and stress – during a critical window of brain development might influence obesity risk.

The research team, led by Harry MacKay, PhD, a postdoctoral associate in pediatrics-nutrition at Baylor, focused on a tiny section of the brain called the arcuate nucleus of the hypothalamus, which regulates the body's energy balance between food intake, physical activity and metabolism.

They studied mice in the first few weeks of life and found that the arcuate nucleus undergoes extensive growth in a critical window of time when brains are particularly sensitive to programming, which will later determine how well the body senses whether it is hungry and when the body has enough food.

The scientists focused on epigenetics and worked to bookmark which genes would and would not be used in different cells. A big surprise in the research came when the investigators compared their epigenetic data in mice to human data and found that the regions targeted for epigenetic maturation in the mouse arcuate nucleus overlapped strongly with human genomic regions associated with BMI.

Waterland says that even though the work did not address when the epigenetic changes happen in humans, previous research has shown it happens earlier in humans than in mice. "My hunch is that the same epigenetic development that we have documented in the early postnatal mouse actually occurs during late fetal development in humans."

If that is the case, "A big, big concern is the very high prevalence of maternal obesity in the US and many developed countries in the world," which may be affecting the health of new babies.

If future weight problems begin before birth or in those first weeks of life, some might feel doomed to a fate of obesity. But Waterland says the focus on genetics in earlier research wasn't particularly encouraging either since it's very difficult to change your genetics. "At least if we understand how environment affects development then at least we can look for ways to improve this in the future," he adds.

It's too early to say whether obesity is actually a neurodevelopment disorder, Waterland explains, but if early research like this continues to build evidence, public health interventions to curb the worldwide obesity epidemic could focus more on prenatal and early life nutrition, healthy weight gain and stress reduction.

Sources:

Science Advances: "Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index."

Robert Waterland, PhD, professor of pediatrics-nutrition, Baylor College of Medicine, Houston, TX. 

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