Genetic Link to Obesity Could Be Key to Treatment of Diabetes and Heart Disease

Following the recent discovery of the obesity-related KLF14 gene, researchers from King’s College London and the University of Oxford have now revealed the exact master regulator gene that controls the obesity-causing behavior of distant genes inside fat cells linked to type 2 diabetes and cholesterol. The details of the analysis can be found in the journal Nature Genetics.

Although KLF14 was previously identified and linked to the cause of obesity, until now it has remained unclear as to just what role the gene played. The authors of the latest study are hopeful that their discovery will be helpful in developing more effective treatments of such obesity-related illnesses as type 2 diabetes and heart disease, otherwise known as metabolic diseases. They also pointed out that other genes discovered to be controlled by KLF14 are associated with such metabolic traits as body mass index (BMI), insulin and glucose levels, obesity, and cholesterol.

For their study, the researchers gathered fat samples from under the skin of 776 female twins in Great Britain, and then analyzed more than 20,000 genes within the fat cells. The findings revealed that KLF14 strongly influences the behavior of distant genes that exist inside fat tissue. To confirm their findings, the research team collected and analyzed 600 additional fat samples taken from a group of people in Iceland resulting in the same findings.

Because fat plays a major role in susceptibility to obesity, heart disease and diabetes, the development of medications that target KFL14 could lead to highly effective treatments for metabolic diseases.

According to lead study author, Tim Spector, of King's College London, “This is the first major study that shows how small changes in one master regulator gene can cause a cascade of other metabolic effects in other genes. This has great therapeutic potential particularly as by studying large detailed populations such as the twins we hope to find more of these regulators.”

Although our offspring inherit a set of genes from both parents, the active copy of KLF14 is inherited from the mother, as the father’s copy is switched off. Therefore, the ability of KFL14 to control other genes is dependent on the copy of the gene inherited from the mother, meaning that the mother passes on the master switch of obesity. Co-leader of the study, Mark McCarthy, from the University of Oxford, noted, “KLF14 seems to act as a master switch controlling processes that connect changes in the behaviour of subcutaneous fat to disturbances in muscle and liver that contribute to diabetes and other conditions. We are working hard right now to understand these processes and how we can use this information to improve treatment of these conditions.”

The number of obese individuals worldwide has doubled since the 1980s, with one in ten adults now being obese. Almost two-thirds of the adult population in the UK is either overweight or obese, while in the U.S., metabolic diseases account for about 10 percent of the American healthcare budget. In addition, the number of people who suffer from type 2 diabetes continues to rise, after having already reached epidemic proportions. Lack of exercise and poor diet are the main culprits for many who suffer from obesity and metabolic diseases.