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Diet drug fools the gut – U

A potential weight-loss drug developed by a team of San Diego scientists tricks the body into thinking it’s been fed.

The drug, called fexaramine, doesn’t decrease appetite, but it does increases burning of calories and triggers other responses that control weight.

Tested in mice, the drug caused the gut to react as if it had been given a meal, controlling weight, reducing cholesterol levels and blood sugar. It also turns white fat, which is relatively unhealthy, into the more benign brown fat.

In people, the drug could not only treat obesity, but Type 2 diabetes and related conditions.

‘Imaginary Meal’ drug

Fexaramine has a safe method of action, so a rapid start to human clinical trials is feasible, said study leader and Salk researcher Ron Evans.

Evans is senior author of the study, published Monday in Nature Medicine. Sungsoon Fang, also of the Salk, was first author. The study is available at: utsandiego.com/imaginarymeal.

He described the drug as acting like an “imaginary meal,” producing signals that get the body read for digestion, even though it has no calories.

“It doesn’t block the appetite center,” Evans said in an interview Monday. “So our mice basically eat the same amount, but they get a big benefit in battling metabolic disease, because the drug triggers a very robust response to improve liver function, and to enhance the metabolic activity of adipose or fat tissue to burn more fat. But it doesn’t have calories.”

Metabolic disease or syndrome, closely linked to Type 2 diabetes, causes a cluster of health problems, such as excess weight gain around the waist, increased blood pressure, and high cholesterol levels.

Fexaramine also reduces chronic inflammation, linked to diabetes and obesity, Evans said.

“Any of those effects would be beneficial to people,” he said. “The improved safety of a drug that doesn’t get into the body, but one which the body knows is there, means there’s a good chance it can move quickly toward clinical trials.”

About 200 mice were used for the main study. They didn’t actually get a pill, Evans said; people will take pills, not mice. Instead, the drug was given to the mice in powdered form, into their food. It acted as a food extender, simulating the effects of a greater meal. The drug was also given on its own.

The gut is naturally selective about what it will absorb, Evans said, and fexaramine doesn’t get past the intestine. Yet its contact with the intestinal lining is enough to trigger the metabolic responses involved in digestion.

Dr. Ken Fujioka, a weight-management and metabolic specialist at Scripps Health, said the study is good, but success in people is hard to predict.

“This is a very interesting target for weight loss and the effect in mice is excellent and the science is very good,” Fujioka said by email. “The big question is will this translate into humans and unfortunately this is a crap shoot. Many very good ideas and molecules worked great in mice but not in humans.”

Fujioka said the effect of turning white fat to brown fat is of special interest, as it’s easier to lose brown fat than white.

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