Obesity has rapidly expanded in recent decades to affect more than 2 billion people, making it one of the leading causes of poor health worldwide. Many people continue to struggle to lose weight despite decades of research on diet and exercise regimens. Researchers at Baylor College of Medicine and other affiliated institutions believe they have discovered why, and they believe we must shift our focus from obesity treatment to prevention.
The team finds in the journal Science Advances that early brain development molecular pathways are likely a major factor of obesity risk. Previous big human investigations have suggested that the genes most significantly associated with obesity are expressed in the developing brain. The current mouse study focused on epigenetic development. Epigenetics is a molecular bookmarking mechanism that governs which genes are used or not 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 significant long-term impact on health and disease,” said corresponding author Dr. Robert Waterland, a professor of pediatrics-nutrition and a member of Baylor’s USDA Children’s Nutrition Research Center.
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“Body weight regulation is very sensitive to such ‘developmental programming,’ but exactly how this works remains unknown.”
“In this study, we focused on 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 at the time.
“During early postnatal life, the arcuate nucleus undergoes substantial epigenetic maturation, according to our findings. This time period is also extremely susceptible to developmental programming of body weight management, implying that these consequences could be the result of dysregulated epigenetic maturation.”
The researchers looked at both DNA methylation (a key epigenetic marker) and gene expression before and after the postnatal crucial window for body weight development had closed.
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“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.”
“This is the first study to examine epigenetic development in males and females,” Waterland added. “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.”
(With Inputs From ANI)
