Obesity is the modern disease. Someone defines it as a pandemic, especially if we consider the number of people affected by it, and the increase in recent years. There are more than two billion obese people in the world, according to estimates, and lifestyle is not the only cause. Together with this, in fact, it is increasingly clear that genetics play a fundamental role in regulating the body mass index, and in determining the ability to manage the sense of hunger and satiety and to regulate calorie intake accordingly.
According to a new study published in Science Advancesthen, the epigenetic development of a particular region of the brain known to be crucial for the regulation of body weight, would also be decisive. Everything would play out, in fact, during the development and formation of this area of the brain. In this phase, some wrong eating behaviors or exposure to severe stress could lead to a predisposition to obesity.
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The link between obesity and development
Several studies in recent years have found a link between obesity and brain development. For example, it has been shown that transient environmental influences (such as nutrition or stress) during critical developmental periods can have an important and permanent impact on body weight regulation. Extensive genetic studies conducted on samples of hundreds of thousands of people then identified gene regions associated with the body mass index. The genes identified in these studies begin to express themselves in the developing brain.
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The right brain region to investigate
The research focused on a small section of the brain called the arcuate nucleus of the hypothalamus, which regulates the body’s energy balance between food intake, physical activity and metabolism. In the case of rodents, this region grows a lot in the first weeks of life, during breastfeeding, a critical period in which the brain is particularly sensitive to external “programming”.
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In this period, in fact, the epigenetics of the energy balance is defined in the arcuate nucleus of the brain, which will later determine the body’s ability to perceive if it is hungry and when it has enough food. In the case of men, however, this phase occurs a little earlier, when the fetus is in the terminal stages of its development before birth. In this case, the role of the mother would be decisive.
The role of epigenetics
The key that allowed to establish a parallelism between mice and humans is precisely epigenetics. It deals with the study of which characters – among those encoded by the genetic code – are expressed in a cell, and how their expression is influenced by behavior and the environment. In the study, in particular, the scientists were able to characterize the epigenetic changes that occurred in the brains of rodents and that concerned the regulation of body weight. By comparing the epigenetic data of the mice with those of humans, the researchers found that the regions involved in the maturation of the arcuate nucleus of the mice were perfectly superimposable to the human genomic regions associated with the body mass index.
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The only difference between the two species, in fact, is that in humans the development of this part of the brain occurs before birth. Changing genetics isn’t possible, but acting on environmental conditions that affect gene expression is, and that’s what the authors hope to achieve from this study.
“Many neurodevelopmental milestones occur earlier in humans than in mice,” he says Robert Waterland, professor in the Department of Pediatrics and Molecular and Human Genetics at Baylor College of Medicine, and author of the study. “So it is possible that the epigenetic maturation we have documented in the early postnatal mouse occurs during late fetal development in humans. In this case, of course, the impact of maternal obesity would be of greater concern.”
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Obesity of the mother, but not only
One of the determining factors for the unborn child, we said, is the state of health of the mother. Not maternal obesity itself, according to the authors, but rather a “signal” of maternal obesity reaching the fetus.
“We still don’t know what this signal (or signals) is,” says Waterland. “Some likely candidates are increased concentrations of glucose or lipids in the maternal circulation, or general inflammation (leukocyte infiltration) associated with obesity.” .
Not only that, even women with a normal body mass index (ie normal weight) should pay attention, because the quality of the “bricks” that the body uses for the development of the fetus depends entirely on the mother’s diet. “Pregnancy – continues Waterland – is therefore an excellent time to try to improve eating habits. Furthermore, any potential toxins (such as alcohol and cigarette smoke) should be avoided regardless of body mass index”.
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Is it possible to think of an intervention plan?
If the association between brain maturation, obesity and specific risk factors were to be confirmed, according to the authors it would be possible to set up real intervention plans to avoid the “hereditary” component of the disease. A bit like what happened in the past in the case of spina bifida, where folic acid deficiency in the months prior to pregnancy and at the time of conception was a determining risk factor, and folic acid supplementation is become the most effective form of prevention.
Obesity as a neurodevelopmental disease
To cure the obesity epidemic around the world, the authors say at the end of the article, it is important to start recognizing it as a neurodevelopmental disease. One of the risk factors, for example, is the obesity of the mother during pregnancy, but it is not the only one. Severe stressful events, the mother’s concern for food or denial of it can also negatively affect the determination of genetic expression linked to obesity.