Science: Obesity is a neurodevelopmental disorder, early brain development or the main determinant of obesity

Written by nagashi

Editor Wang Duoyu

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In recent decades, the global prevalence of obesity has risen rapidly, affecting more than 2 billion people, making it one of the biggest causes of
poor global health.
However, despite decades of research by scientists on diet and exercise therapy, many people are still stuck in the throes
of losing weight.

Notably, classical studies in mice and humans have shown that during critical periods of early development, nutritional status can permanently alter the body's energy balance regulation and lead to obesity, a phenomenon known as "developmental programming
.
"

Recently, researchers at Baylor College of Medicine in the United States published a report titled "Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpointshuman genomic regions associated with body mass.
" Index's research paper.

The study suggests that the molecular mechanisms of brain development early in life may be a major determinant
of obesity risk.
The team found that epigenetic maturation after birth has significant cell type and sex specificity and occurs in genomic regions
rich in human body mass index.

Recent genome-wide association studies have shown that the genes most closely associated with obesity are expressed
in the developing brain.
This means that obesity is more like a neurodevelopmental disorder that is strongly influenced by nutrition in a key ontogenerative window in an epigenetic way
.

Epigenetics is a molecular marker system that allows two individuals with exactly the same gene sequence to exhibit traits that vary greatly
.
Previous studies have confirmed that epigenetic mechanisms can regulate neurodevelopment
.
However, scientists know very little
about their role in establishing and maintaining the brain's energy balance circuits.

In the latest study, the team looked closely at a brain region called the hypothalamic arch nucleus (AHR), which is the primary regulator of food intake, physical activity, and metabolism
.
The researchers found that the lower thalamic arch nucleus undergoes extensive epigenetic maturation early after birth, a period that is very sensitive
to developmental procedures for weight regulation.
This suggests that obesity may be the result of
an epigenetic maturation disorder.

Genome-wide analysis of the hypothalamic arch nucleus and RNA-seq
research team performed genome-wide analysis of DNA methylation (an important epigenetic marker) gene expression, respectively during the ant-and-after periods of critical window in obesity risk developmental planning
.
One of the biggest strengths of the study is that it looked at two broad classes of brain cells — neurons and glial cells — which have very different
epigenetic maturations.
Not only that, but the research team also compared the epigenetic development of male and female mice and found a wide range of sex differences
.

The epigenetic maturation
of the subpopulation of the hypothalamic archonuclear neurons was most surprising when the researchers compared their epigenetic data in mice with human data from large genome-wide association studies that screened obesity-related gene variants, the epigenetically mature genomic regions in the mouse hypothalamic arch nucleus highly overlapped
with the human genome region associated with body mass index (BMI).

These associations are associated
with epigenetic maturation of AH neurons after birth with a response to dietary signals, proving that obesity risk in humans is determined in part by the epigenetic development of the
archoid nucleus.
These findings provide new evidence that developmental epigenetics may be linked
to the 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.

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