A study recently published in The New England Journal of Medicine revealed that the FTO gene, which is known to be associated with obesity, plays a role in a master gene control switch mechanism that establishes whether fat cells store or burn fat. The study is entitled “FTO Obesity Variant Circuitry and Adipocyte Browning in Humans” and was conducted by researchers at the Massachusetts Institute of Technology (MIT) and Harvard Medical School.
Obesity is one of the most serious public health problems worldwide, having been associated with the development of medical conditions like heart disease, type 2 diabetes and certain types of cancer. Obesity is estimated to affect over 500 million people worldwide. In the United States, where more than one-third (78.6 million) of the adult population is obese, obesity has a serious economic burden.
“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,” noted the study’s senior author Dr. Manolis Kellis in a news release.
The FTO gene has been reported to be strongly linked to obesity; however, it is not clear how genetic differences in this gene lead to the condition.
In order to address this question, the research team analyzed known gene control circuits from more than hundred tissues and cell types. Remarkably, researchers found a major gene control pathway in human adipocyte progenitor cells (immature cells that turn into fat cells) that controls whether fat cells store or burn calories.
Then, researchers investigated genetic difference in adipocytes (fat cells) from healthy individuals that either had the high-risk version of FTO or the non-risk version. The team found that the high-risk version of FTO activates a key gene control switch that, in turn, activates two other genes called IRX3 and IRX5, which were subsequently found to control thermogenesis in fat cells (process in which energy stores are used to generate heat).
“Early studies of thermogenesis focused primarily on brown fat, which plays a major role in mice, but is virtually nonexistent in human adults. This new pathway controls thermogenesis in the more abundant white fat stores instead, and its genetic association with obesity indicates it affects global energy balance in humans,” explained the study’s lead author Dr. Melina Claussnitzer.
Interestingly, the team found that it was possible to manipulate this pathway in cells from mice and humans with the high-risk obesity version, switching off IRX3, IRX5, genes that promote fat storage, and restoring thermogenesis.
“By manipulating this new pathway, we could switch between energy storage and energy dissipation programs at both the cellular and the organismal level, providing new hope for a cure against obesity,” concluded Dr. Kellis.
The team believes that their findings may lead to the development of new strategies to prevent and treat obesity, and that it provides evidence that genetic differences between individuals may control how the body stores and burns fat. The authors are planning to establish collaborations with research centers and industry partners in order to apply their findings in a clinical setting.