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Drug for overactive bladder may help people lose weight, too

Drug for overactive bladder may help people lose weight, too


Brown fat, which burns energy, is hitting mainstream drug development in a big way

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 Brown fat cells (stained brown with antibodies against the brown fat-specific protein Ucp1) nestled in amongst white fat cells.
Brown fat cells (stained brown with antibodies against the brown fat-specific protein Ucp1) nestled in amongst white fat cells.
Patrick Seale, University of Pennsylvania School of Medicine

A drug the US Food and Drug Administration has already approved to treat overactive bladder may also help patients lose weight, a small study shows. The compound is called mirabegron, which is sold by Astellas Pharma as Myrbetriq for overactive bladder. In a 12-man pilot study, researchers found it boosted their ability to burn energy, according to a study in the journal Cell Metabolism.

today's discovery hinges on a specific kind of fatThe drug targets a receptor called the β3-adrenergic receptor. It's expressed in a variety of places, like the bladder — but also on fat cells. That's what led the researchers to wonder if the compound might aid in burning energy. So the scientists gave 12 male volunteers four times the approved dose of Mybetriq. In all 12, the drug boosted metabolic activity, and increased the number of calories they burned while resting by an average of 200 calories at the peak of the drug's effectiveness. Over time, that works out to about an extra pound of fat burned off every two and a half weeks — without any additional effort. That is, assuming there aren't any complicating factors, says study author Aaron Cypess, who conducted the research when he was at the Joslin Diabetes Center and Harvard University (he is now the section head of translational physiology at the National Institutes of Health). He cautioned that his study was more of a snapshot than a movie; it's not clear what the effects of Myrbetriq are over the course of 12 or 24 hours. That research is next on his list; so is figuring out whether it's possible to induce brown fat activation with a lower dose. In other words: don't try this at home.

Today's discovery hinges on a specific kind of fat. White fat stores energy; brown fat burns it, usually in response to cold. For a long time, scientists didn't realize that adult humans had brown fat — it was thought to exist only in babies. Brown fat helps keep people warm, and it's especially crucial for newborns, who aren't yet capable of shivering to generate heat. Brown fat is brown because it contains more mitochondria — cellular energy powerhouses —than the standard white fat. It's specialized to burn its energy stores for heat. In babies, brown fat is about 5 percent of their body mass, and it's stored around their shoulders and spine.

Image of brown fat activation with Mybetriq (Courtesy Aaron Cypess)

But in 2009, three research groups independently announced they had found brown fat in adults — Cypess, in fact, was a member of one of those groups. Adults have much less of it than babies, with deposits concentrated mostly in the shoulders and neck. Two more papers, from two other groups, followed in a matter of weeks: brown fat was real, and adult humans had it. Shortly after that, the NIH held a meeting to plan research for the new organ, and the financial stimulus bill included funding specifically for the research.

"It was the right kind of synergy between the federal forces of funding, and an academic world that was poised to respond," says Cypess. Now, "there are hundreds of papers being published. It's an explosion."

"It's an explosion."A slew of research into brown fat followed that initial meeting. Some researchers have examined ways to convert white fat to brown fat; other research, like today's, has focused on making brown fat more effective at burning off calories. Yesterday, researchers at Scripps announced a novel compound that also targets brown fat efficiency, though its mechanism of action is different; it's only been tested in mice so far, though human trials aren't far off. They actually hadn't expected the effect, says study author Michael Downes.

"We were familiar with brown fat and pleasantly surprised when we saw this result," Downes says. "It's a great breakthrough, and the question for us now is, can this be translated to humans."

it's the first way to activate brown fat without cold exposureMybetriq also may not be ready for prime-time as a weight loss drug. But it's the first way to activate brown fat without cold exposure, Cypess says. That'll make it easier for scientists to study brown fat, since setting up the cold-exposure studies is difficult and expensive. He also doesn't think drugs that stimulate brown fat will be enough to spur weight loss on their own; rather, he sees them as a tool to make diet and exercise easier for people who are overweight. Brown fat is very good at absorbing blood sugar, which is helpful for people who are diabetic and pre-diabetic; if it can make it easier for those people to make lifestyle changes, that's a positive thing.

The surge of interest is spurred in part by Americans' widening waistlines. More than a third of adults in the US are obese, according to the CDC. Obesity is linked to a number of health problems, most prominently type 2 diabetes, a disorder where the body doesn't process blood sugar. Almost 10 percent of the US population, or 29 million adults, have type 2 diabetes. Obesity also increases risk of heart disease, stroke, arthritis, and some kinds of cancer, according to the National Institutes of Health.