Obesity has increased rapidly in recent decades to affect more than 2 billion people, making it one of the largest contributors to poor health worldwide. Despite decades of research on diet and exercise treatments, many people continue to struggle to lose weight. Researchers anow think they know why, and say we must shift the focus from obesity treatment to prevention.
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. Previous large studies in humans have hinted that genes that are most strongly associated with obesity are expressed in the developing brain. This current study in mice focused on epigenetic development. Epigenetics is a system of molecular bookmarking that determines which genes will, or will not, be used in different cell types.
“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,” said the corresponding author. “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,” said the first author. “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.”
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. “One of our study’s biggest strengths is that we studied the two major classes of brain cells, neurons and glia,” the author said. “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,” the senior author said. “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.”
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,” the author said. “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.”
https://www.science.org/doi/10.1126/sciadv.abo3991
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fsex-specific-epigenetic&filter=22
Is obesity a neurodevelopmental disorder?
- 1,553 views
- Added
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Targeting treatment resistance in chronic lymphocytic leukemia
Read more
Unique tumor-related bacteria tied to young-onset colorectal cancer
Read more
How the tumor escapes therapies
Read more
How one type of lung cancer can transform into another
Read more
How sleepy Acute Myeloid Leukaemia stem cells awaken and grow?
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar