Scientists discover epigenetics behind the desire to exercise using epigenetic couch potato’ mouse
Some people love to exercise while others not. Most of us assumed that its the genetics that plays a role in one’s innate drive to exercise. But a study conducted by researchers from Baylor College of Medicine shows that it’s not genetics, but epigenetics, the molecular level of regulation that determines if one would like to exercise or not.
Epigenetics is the molecular mechanism that controls which genes are turned on or off in different types of cells. Since epigenetics is more malleable than genetics, the study proposes a potential technique to program people to enjoy being physically active.
The Nature Communications reported the Baylor researchers’ novel creation, ‘epigenetic couch potato’ mouse. They observed that alteration in methylation of DNA in the neurons of the hypothalamus in the brain enhances the voluntary exercise behavior. The researchers at the Baylor College of Medicine study developmental programming, the way the environment during development influences the risk of disease in the long term.
The researchers had been studying the developmental programming of energy balance in various mouse models, which is the balance between the calories consumed vs. that is burnedoff, which later lead to the discovery of epigenetics behind one’s desire to exercise.
Surprisingly, while the early environmental influences were infant overnutrition, maternal exercise during pregnancy or fetal growth restriction, the long term effect on energy balance was mostly contributed not by food intake, but by physical activity. The group’s early studies had shown that the early environment that may involve epigenetics affects one’s physical activity ‘set point.’
How the brain regulates energy balance
In the study, Waterland, who also is a professor of molecular and human genetics and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor and his colleagues experimented to test if DNA methylation has any effects on energy balance. They altered the methylation of neuron DNA in a specific region of the brain called the hypothalamus that controls the energy balance of the body. The experiment was done on specialized neurons in the hypothalamus called AgRP neurons, known for their role in regulating food intake.
They inhibited the Dnmt3a gene in AgRP neurons in mice to disrupt the DNA methylation. Dnmt3a gene is responsible for the methylation of DNA in the brain during postnatal life. As expected, the inhibition of the Dnmt3a gene leads to a significant decrease in methylation. Later the scientists observed if these mice gained or lost weight.
Dr. Harry MacKay, a postdoctoral fellow in the Waterland lab, said that they were expecting significant changes in the weight of these mice. But they were disappointed as only a slight increase in the weight was shown by the mice.
They tried to find the root cause of this. They observed the food intake between the normal and Dnmt3a deficient mice. They couldn’t find any. But they saw a significant change in the physical activity of mice.
The researchers introduced running wheels in the cages of mice and observed them for eight weeks. They found that normal male mice ran about 6 Km (3,7 miles) every night, while the Dnmt3a-deficient mice ran only half as much as normal mice and therefore lost less fat. Detailed treadmill studies showed that the Dnmt3a deficient mice were as capable as normal mice for running, but showed less desire.
Their findings propose that epigenetic mechanisms like DNA methylation, established in the brain during fetal or early postnatal life, play a significant role in determining the individual’s desire for exercise. The findings are important as a decrease in physical activity has contributed to the worldwide obesity epidemic.