Scientists have just lately proposed that weight problems is a neurodevelopmental dysfunction.
Over the final a number of many years, weight problems has quickly grown to have an effect on greater than 2 billion individuals, making it one of many largest contributors to poor well being globally. Many people nonetheless have hassle shedding pounds regardless of many years of examine on weight-reduction plan and train regimens. Researchers from Baylor College of Medicine and affiliated establishments now imagine they perceive why, they usually argue that the emphasis must be shifted from treating weight problems to stopping it.
The analysis workforce studies within the journal Science Advances that early-life molecular processes of mind growth are seemingly a serious determinant of weight problems threat. Previous massive human research have proven that the genes most strongly related to weight problems are expressed within the growing mind. This most up-to-date examine in mice centered on epigenetic growth. Epigenetics is a molecular bookmarking system that regulates whether or not genes are utilized or not in sure cell varieties.
“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,” mentioned corresponding creator 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,” mentioned first creator Dr. Harry MacKay, who was a postdoctoral affiliate within the Waterland lab whereas engaged on the undertaking. “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 carried out genome-wide analyses of gene expression and DNA methylation, a key epigenetic tag, 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.”
The human connection
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,” MacKay 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.”
Reference: “Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index” by Harry MacKay, Chathura J. Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa and Robert A. Waterland, 28 September 2022, Science Advances.