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For some people, losing weight can be tricky, no matter how much they diet or exercise. Scientists from Baylor College of Medicine and other institutions have proposed an explanation: Obesity is actually a neurodevelopmental disorder.

In a new study, published Sept. 28 in the journal Science Advances, scientists found brain development likely plays a major role in a person's risk for obesity. If that is true, people could be predisposed to being obese, said Dr. Harry MacKay, a former postdoctoral associate at Baylor and the study’s first author.

“This is something that is established long before you ever have any say in the matter. This isn't necessarily because you are weak willed,” said MacKay, who is now a behavioral scientist in Canada. “It's difficult to lose weight because you're fighting against stuff that was ingrained in your brain’s architecture.”

That ingraining may occur during the late stages of fetal development in humans, though more research is needed to confirm that, said Dr. Robert Waterland, a professor of pediatrics and nutrition and member of the USDA Children’s Nutrition Research Center at Baylor.

If it does occur late in fetal development, a pregnant person’s body mass index (BMI) and nutrition could limit the chance obesity will pass from one generation to the next, Waterland said.

“If maternal obesity actually promotes obesity in children, then what happens over generation after generation is that this is just going to snowball and get increasingly worse,” he said.

Experts have long known that obesity during pregnancy was linked to a host of negative consequences, said Dr. Cindy Celnik, an OB-GYN at The Woman’s Hospital of Texas. Prior studies have linked obesity during pregnancy to a higher risk that a child will develop various health problems like congenital disorders, growth problems, childhood obesity and childhood asthma, according to the Mayo Clinic.

“We think that what's happening in utero is that nutritional excess … can lead to permanent changes in the metabolic pathways of your child,” she said. “And that's what really increases your child's risk of not just obesity, but high blood pressure later in life.”

The prevalence of obesity has been increasing for decades; the World Health Organization said last year that the number of adults considered obese has nearly tripled since 1975. In the United States, a 2020 survey from the National Center Health Statistics found more than 42 percent of adults were considered obese.

Obesity is a major risk factor for a host of poor health consequences, including heart disease and stroke, diabetes, arthritis and certain cancers.

MacKay estimated that half of a person's typical body weight is determined by genetics. The rest is determined by other factors, and it’s likely that brain development plays a significant role, he said.

“Whatever it is that establishes your kind of ‘target body weight,’ or your appetite, or whatever you want to call it, it has to be something that happens early, before you really have a lot of control over it,” he said. “Because it's just so pervasive, it's so hard to resist once it’s set.”

In Waterland’s lab at Baylor, scientists study how nutrition during critical periods of development — embryonic, fetal and early postnatal life— can have a permanent effect on metabolism, health and risk for disease. Scientists refer to this area of study as “developmental programming.”

There has been extensive research on the effect developmental programming can have on obesity, and BMI in general, Waterland said. Back in 2016, a study in The Lancet found that obesity during pregnancy can increase a child’s risk for obesity.

Researchers in Waterland’s lab are trying to pinpoint when the developmental programming linked to weight gain occurs. To do so, they studied mice during the suckling period, the several weeks after they’re born that are key for developmental programming.

The researchers focused on a region of the brain called the arcuate nucleus of the hypothalamus, which acts as a “master regulator” influencing appetite, metabolism and the energy available for physical activity. They discovered the arcuate nucleus undergoes extensive epigenetic programming — or changes in the way genes work — during a mouse’s suckling period, and is also very sensitive to developmental programming of body weight regulation. They also found that many of the epigenetic changes happened earlier in females than in males.

While comparing their findings to data from human studies that screen for genetic variants associated with obesity, researchers found an overlap between the regions they studied in mice and the human genomic regions associated with BMI.

That suggests a person’s risk for obesity is partly determined by epigenetic development in the acuate nucleus, Waterland said.

“Our current findings show a very, very clear link to human biology,” Waterland said.

Confirming exactly when the developmental programming occurs will be difficult, because scientists will need to study human brains, which can only occur after a miscarriage or the death of a child. Waterland said he’s hopeful his team can study brain tissue collected as part of previous studies, but he estimated it could still take at least five years to find an answer.

In the interim, Waterland and MacKay said the new study reaffirms the importance of addressing the core problem of obesity.

Celnik said it can be difficult to talk patients about obesity, but she encourages those who are trying to become pregnant to do their best to lose weight if they're overweight or obese. Obesity during pregnancy also increases risks for complications such as miscarriage, gestational diabetes and preeclampsia.

"Losing a little bit of weight can have a big beneficial impact on your pregnancy and on your baby," she said.

Waterland and MacKay said public health services could be the key to reducing widespread obesity. Earlier research has linked the prevalence of obesity to socioeconomic issues, such as food insecurity and poverty.

“Smoothing over any gaps that society isn't covering produces big benefits in life, because then you will have a child who is destined to live a healthier life all the way until they're 90 years old,” MacKay said.