Anti-Obesity Drug Target Could Burn Calories Even While the Body Rests

They secret to the long-awaited anti-obesity pill could be buried deep on chromosome 21, where scientists believe a single gene might be preventing the body from burning up extra calories at rest. If we can find a way to target that gene, new research suggests, exercise and dieting could become obsolete, at least when it comes to fat loss.

The body is always burning calories, but this research, published in EMBO Reports, suggests a weight loss pill could increase the number of calories the body burns at rest by targeting one gene called RCAN1.

Led by Damien Keating, Ph.D., a research fellow at Flinders University’s Centre for Neuroscience, this study suggests that RCAN1 works as a “brake” on resting energy expenditure. When he knocked that gene out in a population of mice, they resisted weight gain, even after eating high-fat diets for 25 weeks.

Buoyed by his successful study, Keating is developing a drug that can target RCAN1 and essentially take biology’s foot off that brake, kicking the body into a high-energy-burning cruise control.

“We know that diet and exercise are the best way to lose weight and to maintain a healthy weight range. But we also know that a lot of people struggle to do this successfully and hence we have a rising obesity epidemic around the world,” Keating tells Inverse.

“If we can target the pathway we have recently identified then we would hope that this might increase the number of calories our body burns, even at rest, to help people lose weight that they would otherwise struggle with.”

Keating makes it very clear that a drug based on the activity of RCAN1 won’t materialize for years, as it would have to go through many rounds of safety testing. But his mouse study is a solid start. In the mice he genetically manipulated to not express RCAN1, there was a difference in the way their bodies expended energy in both muscle tissue and fat tissue. In this way, his RCAN-1 targeting strategy increases energy expenditure in two different ways. In muscle cells, RCAN1 can increase energy usage at rest. In fat cells, the effect is similar but slightly more complex.

"“Ideally, it could be something people take each day to help them lose weight."

RCAN1 affects two types of fat: “White fat” cells, which primarily store energy and accumulate in some unwanted places, and “brown fat” cells, which expend calories, even at rest. Though there a few different genes that determine the brown or white-fat destiny of fat cells, knocking out RCAN1 seems to impact development at an earlier stage.

“We found that the effect of RCAN1 likely occurs at the level of stem cell precursor cells within fat tissue,” he explains. “RCAN1 appears to affect the ‘type’ of fat cell they become as they mature and differentiate.”

The drug Keating is developing will target RCAN1 on human chromosome 21 and try to mimic the effect of knocking it out through genetic engineering. He has already identified a “a series of compounds” that have potential, which he is testing for safety and potency.

Keating is aware of the promise that his pill holds for people who struggle to lose weight, but he also makes it clear that there’s still nothing that can replace the other benefits of exercise other than weight loss — for instance, cardiovascular health or mental health benefits. But when all else fails, he imagines that his pill might become a partial solution.

“Ideally, it could be something people take each day to help them lose weight,” he speculates.