Obesity May Be a Neurodevelopmental Disorder - Neuroscience News

Summary: Obesity is, in part, determined by epigenetic development in the arcuate nucleus of the hypothalamus.

Findings suggest developmental epigenetics plays a significant role in both environmental and genetic influences on obesity risk.

The team reports in the journal Science Advances that molecular mechanisms of brain development during early life are likely a major determinant of obesity risk.

“We discovered that the arcuate nucleus undergoes extensive epigenetic maturation during early postnatal life.

The team conducted genome-wide analyses of both DNA methylation—an important epigenetic tag—and gene expression, both before and after closure of the postnatal critical window for developmental programming of body weight.

The biggest surprise came when the investigators compared their epigenetic data in mice to human data from large genome-wide association studies that screen for genetic variants associated with obesity.

The genomic regions targeted for epigenetic maturation in the mouse arcuate nucleus overlapped strongly with human genomic regions associated with body mass index, an index of obesity.

“These associations suggest that obesity risk in humans is determined in part by epigenetic development in the arcuate nucleus,” MacKay said.

“Our results provide new evidence that developmental epigenetics is likely involved in both early environmental and genetic influences on obesity risk.

“Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index” by Harry MacKay et al

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

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows

We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk

Our results offer a potential explanation for both the limited ontogenic windows for and sex differences in sensitivity to developmental programming of obesity and provide a rich resource for epigenetic analyses of developmental programming of energy balance