Some people are content with lying on the couch and watching TV, while others need to be active and exercise every day. Could it be due to the difference in genetics, environment, nurture vs. nature, or something else?
In a recent study published in Nature Communications, researchers from the Baylor College of Medicine wanted to examine the relationship between nurture and exercise; specifically the mechanisms responsible for making some people enjoy exercising more than others. The study highlights how epigenetics suggests that nurture is just as vital as nature in determining how an individual develops.
In previous years, the team had studied the effects that obesity, diet and exercise had on development in various mouse models. In this study, they wanted to determine if they could program a so-called ‘couch potato’ mouse without directly altering the individuals’ genetic sequences. The answer was epigenetics, which, although novel, might not come as a surprise to regular readers of this blog.
“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,” said Dr. Robert Waterland, one of the authors of the study and a professor of pediatrics (nutrition) at the USDA/ARS Children’s Nutrition Research Center at Baylor and Texas Children’s Hospital. “Nowadays, as decreases in physical activity contribute to the worldwide obesity epidemic, it is increasingly important to understand how all of this works.”
Take a step back – why does this matter?
The global obesity epidemic is known to be one of the most significant public health crises of our time. Maintaining an active lifestyle is a key component in the prevention of obesity as well as in facilitating good health and weight loss. Therefore, anything we can do to better understand how to set people up for success in their pursuit of an active lifestyle is not just useful, but could bear massive significance for public health.
If an individual’s innate motivation to exercise was hard-wired into their genetic code that would be significant as well since it would reveal a fixed obstacle. But more promising is the actual discovery that individual predisposition toward exercise is a malleable characteristic that can be affected through epigenetics.
How was the study structured?
Waterland and his team worked with mouse models, and were specifically interested to determine whether the DNA Methylation patterns of neurons located in the hypothalamus affected energy balance and food intake, of which this region is known to be a key regulator through Agouti-related peptide (AgRP) neurons.
DNA methylation is an epigenetic mechanism that involves the addition of a methyl group to the DNA by a DNA methyltranseferase (DNMT) enzyme, resulting in altered gene expression. The relationship between DNA methylation and how it can regulate AgRP neuron function make for an attractive starting point for the study.
First, the researchers deleted the Dnnmt3a gene, responsible for DNA methylation in AgRP neurons in early newborn and postnatal brain development. Then, the team examined the patterns of weight changes in these mice compared to normal ones.
“We expected that interfering with DNA methylation in AgRP neurons would result in major changes in the animals’ weight,” noted Dr. Harry MacKay, a postdoctoral fellow in Dr. Waterland’s lab and first author of this paper. “Somewhat disappointingly, however, the Dnmt3a-deficient mice were only slightly fatter than those that were not deficient.” Fortunately, researchers did not give up at this finding. They sought to confirm the cause of the change in energy balance, and hypothesized that the experimental mice and normal mice would show major difference in amount of food take.
What they did not expect were the results they obtained, which showed differences in the amount of physical activity the two groups of mice chose to partake in.
Running wheels were placed in the mouse cages for eight weeks, where the mouse activity was tracked in terms of the nightly distance they ran. While normal mice ran 3.7 miles each night, the experimental mice—with Dnmt3a deleted and less DNA methylation in AgRP neurons—ran half as much and lost less fat. The researchers screened the mice for any sort of physical deficiencies, but found nothing physiologically different in the Dnmt3a-deficient mice versus the normal. The difference was that the Dnmt3a-deficient mice were less motivated to move.
What comes next?
There is a lot ahead for scientists to try and elucidate about what happens downstream of the AgRP neurons that leads to individuals being less active, since this will shed further light on potential points of intervention to boost individual’s motivation for activity.
One player that came into focus for Dr. Waterland’s team was Bmp7, a protein involved in the development of the hypothalamus, which was found to be hypomethylated in their experimental mice but not in normal mice. Bmp7 affects the development of axons, and is also a secreted factor that may affect local methylation as well.
All findings will also need to be confirmed in humans as well. Still, through their findings, Dr. Waterland and his team have opened the door for more understanding—and potential intervention in—the factors contributing to an individual’s activity level, beyond their ability and extending into their motivation for exercise.
Source: MacKay, H., Scott, C.A., Duryea, J.D. et al. (2019). DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice. Nat Commun 10, 5364
Reference: Homa Shalchi. “Scientists create ‘epigenetic couch potato’ mouse”. BCM News- Nutrition. 2 Dec 2019. Web.
