How the heart can regulate energy balance throughout the body

According to a study in the April 27 edition of Cell, Dr. Chad Grueter, a postdoctoral researcher in molecular biology and his team from the UT Southwestern Medical Center have, for the first time, demonstrated the heart's ability to regulate energy balance throughout the body. The finding may lead to more effective therapies for diabetes, heart disease and obesity, which, according to the Centers for Disease Control and Prevention affect tens of millions of people in the U.S. The researchers discovered in a mouse model that feeding mice a high-fat diet meant they could manipulate a heart-specific genetic pathway that prevents obesity and protects against dangerous changes in blood-sugar levels in those with type 2 diabetes. Senior author of the study, Dr. Eric Olson, chairman of molecular biology at UT Southwestern declared: "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." They used genetically changed mice and an experimental drug to manipulate levels of two regulatory molecules in the heart and discovered that MED13, a vital part of a gene pathway in the heart, controls whole-body metabolism while miRNA-208a, a heart-specific microRNA, blocks MED13s actions. The findings demonstrated that mice with either genetically or drug increased MED13 levels were lean and with elevated levels of energy, whilst those mice that were genetically engineered to lack MED13 in the heart had a higher susceptibility to diet-induced obesity. These mice also had an abnormal blood-sugar metabolism and other alterations that were comparable with a group of conditions called metabolic syndrome, which is associated with the development of coronary artery disease, stroke, and type 2 diabetes. MicroRNAs are small snippets of genetic material that were believed to be of little interest given the fact that they were unable to code for the proteins used in body processes like larger strands of genetic material do, however, researches have discovered in recent years that these molecules are key regulators of disease and stress responses in various tissues and identified at least 500 microRNAs. ??Dr. Olson, one of the five co-founders of the biotechnology company miRagen Therapeutics Inc. concludes: "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." The study was built on the original observation that identified the role of miR-208a and its target MED13 in controlling systematic metabolism. Dr. Grueter adds that future studies will investigate how this heart-specific microRNA communicates with cells throughout the body.