Could Obesity Be A Neurodevelopmental Disorder?

According to researchers from the Baylor College of Medicine molecular mechanisms of early brain development likely play an important role in who becomes obese, pointing out that previous studies indicate that genes connected to obesity begin to express themselves in the developing brain after childbirth.

In a university news release corresponding author Dr. Robert Waterland, a professor of pediatrics-nutrition and a member of the USDA Children’s Nutrition Research Center at Baylor said,  “Decades of research in humans and animal models have shown that environmental influences during critical periods of development have a major long-term impact on health and disease.” “Body weight regulation is very sensitive to such ‘developmental programming,’ but exactly how this works remains unknown.”

“In this study, we focused on a brain region called the arcuate nucleus of the hypothalamus, which is a master regulator of food intake, physical activity, and metabolism,” adds first author, Dr. Harry MacKay. “We discovered that the arcuate nucleus undergoes extensive epigenetic maturation during early postnatal life. This period is also exquisitely sensitive to developmental programming of body weight regulation, suggesting that these effects could be a consequence of dysregulated epigenetic maturation.”

Genome-wide analyses of DNA methylation and gene expression were conducted to investigate obesity’s link to the growing brain, and the processes before and after a critical window in developmental programming for body weight among postnatal mice. 

“One of our study’s biggest strengths is that we studied the two major classes of brain cells, neurons and glia,” MacKays explains. “It turns out that epigenetic maturation is very different between these two cell types.”

“Our study is the first to compare this epigenetic development in males and females,” Waterland says. “We were surprised to find extensive sex differences. In fact, in terms of these postnatal epigenetic changes, males and females are more different than they are similar. And, many of the changes occurred earlier in females than in males, indicating that females are precocious in this regard.”

According to the researchers they discovered similarities between the epigenetic data in mice and human genetic changes linked to obesity. They report that the genomic regions targeted for epigenetic maturation in mouse arcuate nucleus’ surprisingly matched up with human brain regions connected to body mass index (BMI) with clear similarities. 

“These associations suggest that obesity risk in humans is determined in part by epigenetic development in the arcuate nucleus,” MacKay reports. “Our results provide new evidence that developmental epigenetics is likely involved in both early environmental and genetic influences on obesity risk. Accordingly, prevention efforts targeting these developmental processes could be the key to stopping the worldwide obesity epidemic.”