Over the past several decades, obesity has rapidly expanded to impact more than 2 billion people, making it one of the biggest causes of ill health globally. Many people still have trouble losing weight despite decades of study on diet and exercise regimens. Now that they believe they know why, scientists from Baylor College of Medicine and other institutions argue that prevention should take precedence over obesity treatment.
The research team claims in the journal Science Advances that early-life molecular processes of brain development are probably a significant factor in the risk of obesity. Large human research conducted in the past have suggested that the developing brain expresses the genes most strongly linked to fat.
Epigenetic development was the main focus of the most recent mouse study. Epigenetics is a molecular bookmarking mechanism that controls which genes are utilised or not in certain 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 corresponding author Dr. Robert Waterland, professor of pediatrics-nutrition and a member of the USDA Children’s Nutrition Research Center at Baylor. “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 first author Dr. Harry MacKay, who was a postdoctoral associate in the Waterland lab while working on the project. “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 researchers performed genome-wide assessments of gene expression and DNA methylation, two crucial epigenetic tags, both before and after the postnatal critical window for the developmental programming of body weight closed.
“One of our study’s biggest strengths is that we studied the two major classes of brain cells, neurons and glia,” MacKays 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,” Waterland 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.”