Researchers find a possible new route to the prevention and treatment of diabetes during a study of the genomes and epigenomes of lean and obese mice and humans.

obese mouse and lean mouseShare on Pinterest
Researchers compared epigenetic “tags” on fat cells of lean and obese mice.
Image source: Oak Ridge National Laboratory

Diabetes affects hundred of millions of people worldwide with 20.9 million currently diagnosed with diabetes in the US. According to John Hopkins researchers, a new study appearing in the journal Cell Metabolism has collected an abundance of clues as to how genes and the environment unite to trigger diabetes.

The outcomes of the study indicate that obesity-induced changes to the epigenome – the reversible chemical “tags” on DNA that tell a genome what to do – are surprisingly similar in both mice and humans.

Dr. Andrew Feinberg, Gilman Scholar and director of the Center for Epigenetics in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine, says:

It’s well known that most common diseases like diabetes result from a combination of genetic and environmental risk factors. What we haven’t been able to do is figure out how, exactly, the two are connected; this study takes a step in that direction.”

Epigenetic chemical tags affect whether and how often genes are used without changing the genetic code itself. Feinberg has extensively studied the epigenome, which he compares to acting like “software” that runs on DNA’s “hardware.”

Through his research, Feinberg questioned whether epigenetics could explain the high worldwide incidence of type 2 diabetes. Given that obesity is a well-established risk factor for type 2 diabetes, Feinberg’s research group teamed with a group led by G. William Wong, PhD, associate professor of physiology in the Center for Metabolism and Obesity Research at Johns Hopkins, to investigate the epigenetics of otherwise identical mice that were fed either normal or high-calorie diets.

The researchers analyzed epigenetic marks at more than 7 million sites in the DNA of the mice’s fat cells; clear differences were found between the normal and obese mice.

Some of the sites that bore chemical tags called methyl groups in the lean mice were absent in the obese mice and vice versa. The methyl groups prevent genes from making proteins.

Feinberg’s team and colleagues at Sweden’s Karolinska Institutet tested whether the same pattern of differences held in fat cells from lean and obese mice were also present in humans – the results were positive.

“Mice and humans are separated by 50 million years of evolution, so it’s interesting that obesity causes similar epigenetic changes to similar genes in both species,” Feinberg comments. “It’s likely that when food supplies are highly variable, these epigenetic changes help our bodies adapt to temporary surges in calories. But if the high-calorie diet continues over the long term, the same epigenetic pattern raises the risk for disease.”

Also revealed from the research is evidence that some of the epigenetic changes associated with obesity affect genes already known to raise diabetes risk. Other changes affect genes that had not been conclusively linked to the disease, but that turned out to have roles in how the body breaks down and uses nutrients, a process called metabolism.

“This study yielded a list of genes that previously have not been shown to play a role in diabetes,” says Wong.

In further tests, we showed that at least some of these genes indeed regulate insulin action on sugar uptake; they offer insights into new potential targets for treating type 2 diabetes.”

Feinberg concludes that in addition to providing insights for drug development, the results also suggest that an epigenetic test could be developed to detect people much earlier on the path to diabetes.

Medical News Today recently reported that a higher intake of yogurt is linked to a lower risk of developing type 2 diabetes.