Obesity Gene Discovery Offers Potential Cure

Obesity Genes Fitness Health
A man crosses a main road as pedestrians carrying food walk along the footpath in central Sydney, Australia, August 12, 2015. More than two billion people worldwide are now overweight or obese. Reuters/David Gray

American scientists have identified how a key 'obesity gene' region works, and may have found a way to turn it off, moving a step closer to finding a cure for the condition, which affects 500 million people worldwide.

In new research published by the New England Journal of Medicine on Wednesday, scientists at Harvard and MIT found that by tweaking certain pieces of the DNA code in the gene region responsible for coding the fat mass and obesity-associated protein—known popularly as the "FTO gene" or the "obesity gene"—they could cause the body to accelerate metabolism and burn excess fat that otherwise would have remained stored.

Researchers have been aware that certain variants of the FTO gene were connected to obesity since 2007 but were yet to understand the mechanisms of causality. To test how exactly faulty genetics were at play in weight gain, the researchers took fat samples from Europeans holding both the variant of the FTO gene region linked to obesity and a normal FTO gene.

They discovered that, in those with obesity, the DNA code of the FTO gene was activating two other associated genes, IRX3 and IRX5. Those genes, in turn, were preventing fat from being burnt through a process known as thermogenesis—where fat cells get rid of energy in the form of heat, instead of storing it as fat—that happens naturally in those with healthy FTO gene regions.

This led to testing on mice using the Crispr/Cas9 system, which edits the faulty DNA code to the correct sequence by injecting the Cas9 protein into the body, removing certain strands of DNA. Using this gene editing technique to remove bad DNA code, the scientists were able to install the correct code, thereby preventing the body from storing excess fat.

"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," senior author Manolis Kellis, a professor of computer science and a member of MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) told the university in a press release.

"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," she added.

The process has so far proved successful in reversing obesity in mice and human cells in lab tests but is yet to be tested on humans. Nevertheless, scientific experts have hailed the findings.

"It's a big deal," Dr. Clifford Rosen, a scientist at Maine Medical Center Research Institute and an associate editor at NEJM, told the Associated Press. "A lot of people think the obesity epidemic is all about eating too much," he said. "You now have a pathway for drugs that can make those fat cells work differently."

According to Kellis, having a faulty version of the gene does not necessarily mean that someone will become obese—food and exercise remain factors—but it does increase a person's risk. People with the gene from both their mother and father weighed 7 pounds more on average than those without the gene, she said.

Obesity can lead to a number of medical conditions such as type 2 diabetes, cancer and cardiovascular disease. In the U.S., more than one-third of the adult population are defined as obese while another one-third are classed as overweight. In Britain, a quarter of adults—some 12 million people—are classed as obese.

Obesity Gene Discovery Offers Potential Cure | Tech & Science