Epigenetic sluggards
Why do some people like to play sports, while others prefer to lie on the couch? Previously, it was thought that genetics was to blame, but a new medical study on mice conducted at Baylor College of Medicine, Texas, for the first time showed that another molecular level of regulation of gene expression – epigenetic – plays a key role in determining the innate craving for exercise.
Epigenetics It includes molecular mechanisms that determine which genes will be turned on or off in different types of cells. Because epigenetic mechanisms are inherently more manageable than genetic ones, the findings provide a potential way to "program" people to enjoy physical activity.
Researchers have reported the creation of "epigenetic mice". They found that changes in DNA methylation in hypothalamic neurons have a significant effect on voluntary exercise behavior.
Over the past few years, researchers have studied programming the balance of calories consumed and burned in various mouse models. A long-term positive energy balance leads to obesity, regardless of whether the individual had early slow fetal growth, excessive nutrition in childhood or intense physical activity in the mother during gestation. It is noteworthy that the energy balance is strongly associated with the level of physical activity of an individual, and not with food intake.
Earlier studies by the authors have shown that the environment can influence the establishment of physical activity levels, and the role of epigenetics has also been suggested.
In the current study, Robert Waterland and his colleagues conducted an experiment to test whether DNA methylation in brain cells affects energy balance. They focused on the hypothalamus because it plays an important role in energy balance, and specifically studied the AgRP neurons that regulate the amount of food consumed.
The researchers disrupted DNA methylation in AgRP neurons by turning off the Dnmt3a gene, which is responsible for adding methyl groups to DNA in brain cells in the early postnatal period of life. The results showed that DNA methylation in the AgRP neurons of these mice significantly decreased. The researchers then checked whether these animals gained or lost weight compared to normal mice.
Contrary to expectations, mice with the Dnmt3a gene turned off were only marginally fatter than control mice. But when researchers began to search for the cause of the change in the energy balance, everything became more interesting. The group expected to find differences in food intake between normal mice and mice with the Dnmt3a gene turned off. But there were none. But there was a big difference in voluntary spontaneous physical exercises.
The researchers placed running wheels in the animals' cages for eight weeks and measured how much they run each night. Males of normal mice ran about 6 km per night, while mice with the Dnmt3a gene turned off ran half as much and, accordingly, lost less fat. Detailed studies have shown that although mice with Dnmt3a deficiency ran twice as far as normal mice, they were just as capable of running – it seemed that they lacked the desire.
Thus, epigenetic mechanisms for controlling gene expression, such as DNA methylation, which are established in the brain during prenatal development or in early childhood, play an important role in the formation of a tendency to exercise. As reduced physical activity is currently contributing to the global obesity epidemic, understanding these processes is becoming increasingly important.
Article H.MacKay et al. DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Baylor College of Medicine: Scientists create an 'epigenetic couch potato' mouse.