At the start of a meal, FXR prepares for an influx of food, not only triggering bile acid release but also altering blood sugar levels and instigating the burning of some fats.
Other drugs have been developed that act on FXR pathways, but they affect several organs and have unwanted side effects. An important feature of fexaramine is that it only functions in the gut and does not dissolve into the blood like appetite suppressants or caffeine-based diet drugs.
Since it does not reach the bloodstream, it is likely to be safer than other FXR-targeting drugs, say the researchers who are working to set up clinical trials that will test fexaramine's effectiveness in human patients.
Obese mice given a daily dose of the drug for five weeks stopped gaining weight, lost fat, and had lower blood sugar and cholesterol levels than untreated mice.
They also experienced a rise in body temperature, a sign that their metabolism was ramping up. Some of the deposits of white fat in their bodies were converted into the healthier form of calorie-burning "brown" fat.
The drug even affected bacteria in the guts of the mice, although what these changes mean is not yet clear.
Dr Evans compared fexaramine's effect in the intestine to the start of a relay race.
"The body's response to a meal is like a relay race, and if you tell all the runners to go at the same time, you'll never pass the baton," he said. "We've learned how to trigger the first runner so that the rest of the events happen in a natural order."
Ideally the drug, would work in conjunction with diet and lifestyle changes to combat obesity, said the scientists, whose research is reported in the journal Nature Medicine.
- PAA
