Imaginary meal tricks body to lose weight
Researchers
have created a new type of diet pill that tricks the body into thinking it has
eaten causing it to burn fat. The compound lowered weight, cholesterol and
inflammation in mice during trials
Salk
researchers have developed an entirely new type of pill that tricks the body
into thinking it has consumed calories, causing it to burn fat. The compound
effectively stopped weight gain, lowered cholesterol, controlled blood sugar
and minimised inflammation in mice, making it an excellent candidate for a
rapid transition into human clinical trials.
Unlike
most diet pills on the market, this new pill, called fexaramine, doesn't
dissolve into the blood like appetite suppressants or caffeine-based diet
drugs, but remains in the intestines, causing fewer side effects.
“This
pill is like an imaginary meal,“ says Ronald Evans, senior author of the new
paper, published in Nature Medicine. “It sends out the same signals that
normally happen when you eat a lot of food, so the body starts clearing out
space to store it. But there are no calories and no change in appetite.“
Evans'
laboratory has spent nearly two decades studying the farensoid X receptor
(FXR), a protein that plays a role in how the body releases bile acids from the
liver, digests food and stores fats and sugars. The human body turns on FXR at
the beginning of a meal, Evans and others have shown, to prepare for an influx
of food. FXR not only triggers the release of bile acids for digestion, but
also changes blood sugar levels and causes the body to burn some fats in
preparation for the incoming meal.
Pharmaceutical
companies aiming to treat obesity, diabetes, liver disease and other metab olic
conditions have developed systemic drugs that activate FXR, turning on many
pathways that FXR controls. But these drugs affect several organs and come with
side effects. Evans wondered whether switching on FXR only in the intestines
rather than the intestines, liver, kidneys and adrenal glands all at once
might have a different outcome.
“When you
eat, you have to quickly activate a series of responses all throughout the
body,“ says Evans. “And the reality is that the very first responder for all
this is the intestine.“
Evans and
his colleagues developed the fexaramine compound by departing from the drug
scaffold that most pharmaceutical companies typically pursue when targeting
FXR. “It turns out that when we administer this orally, it only acts in the
gut,“ explains Michael Downes, co-corresponding author. Giving one such drug in
a daily pill form that only reaches the intestines without transporting into
the blood stream that would carry the drug throughout the body not only
curtails side effects but also made the compound better at stopping weight
gain.
When the
group gave obese mice a daily pill of fexaramine for five weeks, the mice
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. Even the collection of bacteria in the guts of mice shifted when
they received the drug, although what those changes mean isn't clear yet.
So, why
does fexaramine in the intestines work even better than drugs that simultaneously
activate FXR throughout the body? Evans thinks it has to do with the natural
order in which the body's molecular pathways normally responds to a meal.
“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,“ says Evans. “We've
learned how to trigger the first runner so that the rest of the events happen
in a natural order.“
Since
fexaramine doesn't reach the bloodstream, it is also likely safer in humans
than other FXR-targeting drugs, the researchers hypothesise. They're already
working to set up human clinical trials to test the effectiveness of fexaramine
to treat obesity and metabolic disease.Ideally the drug, administered under a
doctor's guidance, would work in conjunction with diet and lifestyle changes,
similar to weight-loss surgeries or other obesity or diabetes drugs.
MM 6JAN15
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