Could blocking a single gene cure obesity without diet and exercise?

One of the biggest obstacles that obese people face as they try to lose weight is struggling to stick with diet and exercise plans. Scientists led by Flinders University in South Australia say they might have found a workaround—a single gene that can be blocked to promote weight loss without the need to cut calories or spend hours at the gym.

The team removed a gene called RCAN1 from mice and then fed them a diet high in fat. They did not gain weight, even after they ate as much of the food as they wanted for a long period of time, according to a statement from the university. The researchers published their results in the journal EMBO Reports.

The key here is that blocking RCAN1 helps the body transform unhealthy white fat into calorie-burning brown fat, said team leader Damien Keating, Ph.D., professor of molecular and cellular physiology at Flinders.

“Removing RCAN1 had two major effects,” Keating said in a video about the research (see below). In fat cells, “it reduced the storage of fat in dangerous areas around the belly, for example. And then in muscle it actually [caused] muscles to burn more calories at rest.”

To confirm the benefits of removing RCAN1, the researchers tested several different diets across timelines ranging from eight weeks to six months. They reported that they saw health improvements in the animals in all of those scenarios.

The effort to figure out how to turn white fat brown has inspired a range of innovations. Researchers at the University of Pennsylvania, for example, are working on inhibiting the gene FLCN, which produces a protein that suppresses the browning of fat. And a team at Florida’s Sanford Burnham Prebys Medical Discovery Institute has discovered that increasing signaling among natriuretic peptides in adipose tissue prevents obesity in mice.

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But there have been some failures along the way. Ember Therapeutics, which was founded in 2012 on the promise of using the protein BMP-7 to stimulate brown-fat production, shut down three years later.

The Flinders team has developed drugs that target the protein made by the RCAN1 gene. They are now testing them to see how effectively they inhibit the gene and whether they can be developed into medicines to treat people.

“The ideal would be to take some sort of pill that didn’t require you to watch your diet, that didn’t require you to exercise,” Keating said in the video. “Now, that might seem like a pipe dream, but the findings that we have out of this mouse study at least indicate a novel pathway that we might be able to target,” he said.