Manipulating heart-specific gene pathway may treat obesity, diabetes

In a recent study, scientist has shown that heart can potentially regulate the balance of energy in the body that may prove very useful for the effective treatment of diseases like obesity, diabetes, and heart disease.

Using mice fed a high-fat diet, Researchers from UT Southwestern Medical Center used mice and fed a high-fat diet and found that manipulating a heart-specific genetic pathway is capable of preventing one from obesity and also protects against the harmful changes in the blood-sugar that are mainly associated to type 2 diabetes.

"Obesity, diabetes, and coronary artery disease are major causes of human death and disability, and they are all connected to metabolism. This is the first demonstration that the heart can regulate systemic metabolism, which we think opens up a whole new area of investigation," said Dr. Eric Olson, chairman of molecular biology at UT Southwestern and senior author of the study.

Dr. Chad Grueter, a postdoctoral researcher in molecular biology is the Lead author of the Cell paper.

The study used genetically altered mice and an experimental drug to examine the levels of two regulatory molecules in the heart.

The scientists found that MED13 that is an important part of a gene pathway in the heart, is responsible to control whole mechanism of the body while miRNA-208a, a heart-specific microRNA, inhibits the action of MED13.

Mice with MED13 levels that were increased either genetically or with the help of drug were lean and have high consumption of energy, the researchers said.

However, it was observed that those mice that were genetically engineered to lack MED13 in the heart displayed an increase in the susceptibility to diet-induced obesity.

These mice also had an abnormal blood-sugar metabolism and other changes that were similar to those of a group of conditions called metabolic syndrome, which is connected to the development of coronary artery disease, stroke, and type 2 diabetes.

MicroRNAs are the small fragments of genetic material with little interest once as they do not code for the proteins used in body processes as the larger strands of genetic material do. However, in the recent years, these molecules have evolved as the key regulators of disease and stress responses in various tissues. Almost 500 microRNAs have been identified.

"Several years ago, our lab focused on this heart-specific microRNA, miR-208a, and then worked with a biotechnology company to develop a drug to inhibit miR-208a. While studying the effects of that drug, we observed that animals treated with the inhibitor seemed to be resistant to high-fat diets but were otherwise healthy," Dr. Olson said.

The present study builds on that actual observation by identifying the role of miR-208a and its target MED13 in regulating systemic metabolism.

The future studies will be based on how this heart-specific microRNA communicates with cells throughout the body, Dr. Grueter said.

The details of the findings appeared in the latest issue of Cell.

-With inputs from ANI