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'Couch potato' mice reveal that epigenetics affects urge to exercise

9 December 2019
Appeared in BioNews 1027

For the first time US researchers have shown that not only genetics but a different level of developmental regulation called epigenetics impacts the innate drive of mice to exercise.

Epigenetics is a molecular mechanism within cells that controls which genes are transcribed and which ones are not, determining which genes are 'turned on' and which ones are 'turned off'.

In this study the scientists found that the methylation of DNA, a process which is known to 'turn genes off', in some neurons in the hypothalamus leads to a decrease in exercise activity.

Corresponding author, Dr Robert Waterland, professor at the USDA/ARS Children's Nutrition Research Centre at Baylor and Texas Children's Hospital said: 'We study developmental programming, which refers to how the environment during development can have a long term impact on risk of disease…our earlier findings suggested that establishment of one's physical activity 'set point' can be affected by early environment, and that this may involve epigenetics.'

Epigenetics is more malleable than genetics and could potentially be altered to increase exercise activity. The scientists investigated a specialised class of neurons in the hypothalamus called AgRP neurons which regulate food intake.

They disabled a gene causing DNA methylation in the AgRP neurons of mice and then tested whether these changes in methylation altered the weight of the animals. Interestingly, they discovered that mice with the disabled gene were slightly heavier.

Intriguingly, the animals did not eat more food than the ones with unchanged DNA methylation. However, the researchers did find a major difference in spontaneous physical exercise. Measuring the distance that the mice ran on a running wheel showed that normal mice ran on average 6 kilometres per night, while the methylation-deficient ones only ran half as much, and thus lost less weight. Notably, the epigenetic changes seemed not to impact the physical ability of the animals to run, but the desire to exercise.

'Our findings suggest that epigenetic mechanisms, such as DNA methylation, that are established in the brain during fetal or early postnatal life, play a major role in determining individual propensity for exercise,' Waterland said. 'Nowadays, as decreases in physical activity contribute to the worldwide obesity epidemic, it is increasingly important to understand how all of this works.'

The work was published in Nature Communications.

DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice
Nature Communications |  2 December 2019
Scientists create 'epigenetic couch potato' mouse
Baylor College of Medicine |  2 December 2019
Scientists Discover The Epigenetics Behind One’s Desire to Exercise
Biotecnika |  5 December 2019
Skipping the Gym? Blame your Epigenome
Genetic Engineering and Biotechnology News |  5 December 2019
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