“Possible Cure” for Genetic Obesity; New Obesity-Related Metabolic Pathway Connected with Long-Implicated FTO Gene Region; Single Base Change Can Switch Between Lean and Obese Signatures in Human Pre-Adipocytes

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. But there may now be a new approach to prevent and even cure obesity, thanks to a study led by researchers at MIT and Harvard Medical School and published online on August 19, 2015 in an open-access article in the New England Journal of Medicine. The article is titled “FTO Obesity Variant Circuitry and Adipocyte Browning in Humans.” “By analyzing the cellular circuitry underlying the strongest genetic association with obesity, the researchers have unveiled a new pathway that controls human metabolism by prompting our adipocytes, or fat cells, to store fat or burn it away. "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," says senior author Dr. Manolis Kellis, a professor of computer science and a member of MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) and of the Broad Institute. The strongest association with obesity resides in a gene region known as "FTO," which has been the focus of intense scrutiny since its discovery in 2007. However, previous studies have failed to find a mechanism to explain how genetic differences in the region lead to obesity. "Many studies attempted to link the FTO region with brain circuits that control appetite or propensity to exercise," says first author Dr. Melina Claussnitzer, a visiting professor at CSAIL and Instructor in Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School.
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