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Obesity: Genetic 'Master Switch' May Control How Much Fat You Burn

First Posted: Aug 20, 2015 08:12 AM EDT

It turns out that there may be a "master switch" that controls obesity. By analyzing the cellular circuitry underlying the strongest genetic association with the condition, researchers have found a new pathway that controls human metabolism by prompting our adipocytes, or fat cells, to store fat or burn it away.

Obesity is one of the largest public health challenges of the 21st century. It affects more than 500 million people worldwide, and obesity costs at least $200 billion each year in the United States alone.

"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," said Manolis Kellis, senior author of the new study, in a news release.

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.

In this latest study, the researchers gathered adipose samples from healthy Europeans carrying either the risk or the non-risk version of the FTO region. They found that the risk version activated a major control region in adipocyte progenitor cells, which turns on two distant genes, IRX3 and IRX5.

In the end, the researchers found that IRX3 and IRX5 act as master controllers of a process known as thermogenesis, which is when adipocytes dissipate energy as heat, instead of storing it as fat.

"Knowing the causal variant underlying the obesity association may allow somatic genome editing as a therapeutic avenue for individuals carrying the risk allele," said Manolis Kellis, one of the researchers, in a news release. "But more importantly, the uncovered cellular circuits may allow us to dial a metabolic master switch for both risk and non-risk individuals, as a means to counter environment, lifestyle or genetic contributors to obesity."

The findings are published in the New England Journal of Medicine.

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