Weight Gain & Brain Connection: Could Obesity Be A Neurodevelopmental Disorder?

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Obesity is still one of the most pressing health problems around the world, ranking fifth in a 2021 survey of people from 30 different countries who were asked about the most significant health problems facing their country. It is estimated that nearly two billion adults globally are currently overweight, making it one of the largest contributors to poor health worldwide.

Many people still have trouble losing weight despite decades of research on diet and exercise regimens. Researchers from Baylor College of Medicine and affiliated institutions studied why, and the results recommended that the focus of obesity research should change from treatment to prevention.

According to a study published in the journal Science Advances, early-life molecular mechanisms of brain development are probably a critical factor in determining the risk of obesity. Their most recent mouse study concentrated on epigenetic development, related to a molecular bookmarking system that chooses which genes will be used or not in various cell types.

What The Study Entails

Research over many years in both human and animal models has demonstrated that environmental factors throughout crucial stages of development have a significant long-term influence on health and disease. A phenomenon like this is called developmental programming, and body weight regulation is susceptible to it. However, there is still much to learn about how it operates.

The arcuate nucleus of the hypothalamus, a crucial regulator of appetite, physical activity, and metabolism, was the subject of the study. They found that early postnatal life involves significant epigenetic maturation in the arcuate nucleus. These effects may result from dysregulated epigenetic maturation during this era because it is also susceptible to the developmental programming of body weight management.

The team performed genome-wide assessments of gene expression and DNA methylation, an essential epigenetic marking, before and during the critical postnatal window for developmental programming of body weight, which occurs immediately after birth.

They found significant sex variations between males’ and females’ epigenetic development. Males and females differ more than they resemble one another in terms of these postnatal epigenetic alterations. Additionally, many alterations happened in females sooner than in males, showing that females are precocious in this area.

The researchers also compared human data from extensive genome-wide association studies that look for genetic variations linked to obesity to the epigenetic information obtained from mice. They discovered that human genomic regions linked to body mass index, an indicator of obesity, and mouse genomic regions targeted for epigenetic maturation in the mouse arcuate nucleus highly overlapped. According to this finding, the arcuate nucleus’s epigenetic development influences human obesity risk in part.

When considered collectively, the study’s findings prove that early environmental and genetic influences on the risk of obesity are likely influenced by developmental epigenetics. Therefore, focusing preventative efforts on these developmental stages may be essential for putting an end to the global obesity epidemic.

The findings support the idea that the suckling period is a crucial window for epigenetic developmental programming of energy balance regulation in the mouse ARH and is the first objective, genome-wide, cell type- and sex-specific examination of epigenetic maturation.

The study’s data offer a framework and a fresh set of target locations for analyzing the epigenetic underpinnings of developmental programming and applying findings from rodent models to humans. The study’s authors believe that this will stimulate attempts to learn more about the developmental factors that influence the risk of obesity.

Journal Reference

MacKay, H., Gunasekara, C. J., Yam, K.-Y., Srisai, D., Yalamanchili, H. K., Li, Y., Chen, R., Coarfa, C., & Waterland, R. A. (2022). Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index. Science Advances, 8(39). https://doi.org/10.1126/sciadv.abo3991 

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