The research suggests that obesity-induced changes to the epigenome (the reversible chemical “tags” on DNA, in essence the software” that runs on DNA’s “hardware.”) are remarkably similar in both mice and humans. These similarities may provide a new route to prevention and treatment of diabetes.
The findings reinforce previously thought connections between the genetic make-up of a person and the environment in terms of the risk of developing type II diabetes. Diabetes mellitus type 2 is a metabolic disorder that is characterized by hyperglycemia (high blood sugar) in the context of insulin resistance and relative lack of insulin (when the body does not produce enough insulin to function properly, or the body’s cells don’t react to insulin.)
With the research, given that obesity is a well-established risk factor for the disease, the researchers studied the epigenetics of otherwise identical mice that were fed either normal or high-calorie diets. Epigenetics refers to heritable changes in gene function that cannot be explained by changes in DNA sequence. Often external — environmental — factors are at play.
By shifting through the epigenetic marks of 7 million sites in the DNA of the each mouse’s fat cells, the scientists discovered distinct differences between the normal and obese mice. Some sites that had chemical tags called methyl groups, which were only found in the lean mice (these tags were absent from the obese mice.) These methyl groups prevent genes from making proteins.
Further study showed that some of the epigenetic changes associated with obesity affect genes already known to raise diabetes risk.
When people who were relatively obese and lean were studied, the same pattern of differences in fat cells was seen. The conclusion was that a similar high-calorie diet, over the long term, leads to a similar epigenetic pattern and one that raises the risk for the occurrence of diabetes.
The genes in question appear to regulate insulin action on sugar uptake. Importantly, they offer insights into new potential targets for treating type 2 diabetes.
The study was undertaken at Johns Hopkins University. The findings have been reported to the journal Cell Metabolism. The paper is titled “Mouse-Human Experimental Epigenetic Analysis Unmasks Dietary Targets and Genetic Liability for Diabetic Phenotypes.”
