Obesity is one of the biggest public health challenges of the 21st century. Affecting more than 500 million people worldwide, obesity costs at least $200 billion each year in the United States alone, and contributes to potentially fatal disorders such as cardiovascular disease, type 2 diabetes, and cancer.
“Obesity has traditionally been seen as the result of an imbalance between the amount of food we eat and how much we exercise, but this view ignores the contribution of genetics to each individual’s metabolism,” study head Manolis Kellis told MIT News. Dr. Manolis is a professor of computer science and a member of MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) and of the Broad Institute.
A solution to obesity may lie in manipulating or turning off “fat genes.” Scientists have been aware of a genetic region known as fat mass and obesity associated gene (FTO), which has been the focus of many studies since its discovery in 2007.
Researchers have found a new pathway that controls human metabolism by prompting our adipocytes (fat cells) to store fat or burn it away. Other studies tried to link FTO region with brain circuits that control appetite or willingness to exercise, said researchers.
“Our results indicate that the obesity-associated region acts primarily in adipocyte progenitor cells in a brain-independent way,” said first author Melina Claussnitzer, medicine instructor at Beth Israel Deaconess Medical Center and Harvard Medical School.
The study results (open access) were published this week in the New England Journal of Medicine
Researchers examined genetic differences in adipocytes by comparing fat samples from healthy Europeans who carried the risk type of FTO and those who did not carry genetic risk for obesity. The study found that the risk FTO turned on adipocyte progenitor cells, which then turned on two genes, IRX3 and IRX5.
IRX3 had been found to be a possible obesity gene in separate research done at the University of Chicago.
After conducting follow-up experiments, the research team found IRX3 and IRX5 act as master controllers of thermogenesis, which is how fat cells burn energy as heat instead of storing fat. Exercise, diet, or even cold weather triggers thermogenesis. People with the genetic predisposition to obesity have the IRX3 and IRX5 genes turned on, which then turns off thermogenesis — leading to fat accumulation and obesity.
The discover may lead to cure to obesity. With gene therapy technology, scientists could manipulate the gene and switch nucleotides in DNA to make the tiny switch that would turn an obese gene signature into a lean one. Researchers have been able to make this switch in mice and in human cells in the laboratory.
