Science Advances' new view: Obesity is a neurodevelopmental disorder

In recent decades, the number of obese people has increased rapidly, affecting more than 2 billion people, making it one of the biggest causes of
poor health worldwide.
Despite decades of research into diet and exercise therapy, many people are still struggling to lose weight
.
Researchers at Baylor College of Medicine and its partner institutions now believe they know why, saying we must shift our focus from obesity treatment to prevention
.

The team reports in the journal Science Advances that the molecular mechanisms of brain development early in life may be the main determinants
of obesity risk.
Previous large-scale studies in humans have shown that the genes most closely related to obesity are expressed
in the developing brain.
Current research in mice has focused on epigenetic development
.
Epigenetics is a molecular marker system that determines which genes will or will not be used in
different cell types.

"Decades of research on human and animal models have shown that environmental influences have significant long-term effects on health and disease during critical periods of development," said corresponding author Dr.
Robert Waterland, "and weight regulation is very sensitive to this 'developmental procedure,' but exactly how it works remains unclear
.
" ”

"In this study, we focused on a brain region called the hypothalamic arch nucleus, which is the primary regulator of food intake, physical activity, and metabolism," said first author Dr.
Harry McKay.
"We found that the archoid nucleus undergoes extensive epigenetic maturation
early after birth.
" This period is also very sensitive to the developmental procedures of weight regulation, suggesting that these effects may be the result of
epigenetic maturation disorders.
”

The team performed genome-wide analysis of DNA methylation (an important epigenetic marker) and gene expression, including analysis before and after the critical window of postnatal weight development planning
closes.
"One of the biggest strengths of our study is that we looked at two broad classes of brain cells, neurons and glia, which have proven to be very different
in epigenetic maturity between the two cell types.
"

"Our study is the first to compare epigenetic development in men and women, and we were surprised to find broad sex differences
.
In fact, in terms of these epigenetic changes after birth, males and females differ more than similarly
.
Moreover, many of the changes occur earlier in women than in men, suggesting that women are precocious
in this regard.
”

Human connection

Most surprisingly, when the researchers compared their epigenetic data in mice with human data from large genome-wide association studies that screen for variants in obesity-related genes
.
The epigenetically mature genomic regions in mouse archocytes are highly overlapping
with those associated with body mass index (obesity indicator) in humans.

"These associations suggest that the risk of obesity in humans is determined in part by the epigenetic development of the archoid nucleus
," McKay said.
"Our findings provide new evidence that developmental epigenetics may be associated
with early environmental and genetic effects of obesity risk.
" Therefore, preventive efforts to target these developmental processes may be key
to stopping the global obesity epidemic.
”