January 6, 2015
Scientists at Westmead Millennium Institute for Medical Research (WMI) have contributed to the development of an entirely new type of pill that tricks the body into thinking it has consumed calories, causing it to burn fat.
Research published in Nature Medicine shows that the pill is effective in stopping weight gain, lowering cholesterol, controlling blood sugar and minimising inflammation.
And because the drug, called fexaramine, acts in the intestine and is not absorbed into the blood, it is expected to cause fewer side effects in humans than other diet pills.
Professor Chris Liddle and researcher Sally Coulter from WMI’s Storr Liver Centre collaborated on the research with a team at the Salk Institute Gene Expression Laboratory in the United States.
Professor Liddle says fexaramine activates a protein called FXR which plays a role in how the body releases bile acids from the liver, digests food and stores fats and sugars.
“What we did with this drug was mimic the way your body reacts when you eat a meal,” said Professor Liddle.
“This pill is like an imaginary or virtual meal and sends out signals that normally happen when you eat a lot of food, so the body starts clearing out space to store it and burns fat in the process. But there are no calories and no change in appetite.”
Obese mice given a daily pill of fexaramine for five weeks stopped gaining weight, lost fat and had lower blood sugar and cholesterol levels than untreated mice.
“In addition, the mice had a rise in body temperature–which signals metabolism ramping up–and some deposits of white fat in their bodies converted into a healthier, energy-burning beige form of the tissue,” said Professor Liddle.
“The drug was actually discovered several years ago and while a positive result wasn’t unexpected, the fact that the degree of improvement we found in mice was so marked was a bit of a surprise.”
Fexaramine could also lead to an effective treatment for obesity-related type 2 diabetes, suffered by over a million Australians.
“During our research it became apparent that this drug was a powerful treatment not just for obesity but also for the type 2 diabetes that these mice get,” said Professor Liddle.
Other drugs have previously been developed to activate FXR, but affect several organs including the liver, kidneys and adrenal glands, causing side effects.
Salk Institute Gene Expression Laboratory director Ronald Evans and the research team investigated whether switching on FXR only in the intestines might have a different outcome.
“It turns out that when we administer fexaramine orally, it only acts in the gut,” says Evans.
“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. And the reality is that the very first responder for all this is the intestine.
“We’ve learned how to trigger the first runner so that the rest of the events happen in a natural order.”
The researchers hypothesise that since fexaramine doesn’t reach the bloodstream, it is likely to be safer in humans than other FXR-targeting drugs.
Subject to further research currently underway it is hoped that human clinical trials might begin within three years.
Professor Liddle cautions, however, that patients taking the fexaramine pill would still need to make diet and lifestyle changes.
“Experience would tell us that no obesity treatment works particularly well unless it is associated with some lifestyle changes. So while I think this pill could be a major step forward in the treatment of both obesity and type 2 diabetes, a healthy diet and lifestyle is always a good accompaniment.”