Losing Weight With The Meal That Never Was

Losing Weight With The Meal That Never Was

 Forget appetite suppression and wild snake oil claims. Weight loss pills are successful when they work with the body's normal processes.Don LaVange, CC BY-SA 2.0

A new pill developed by the Salk Institute may be an answer to the giant, out-of-shape question mark that is the American obesity epidemic. Researchers are calling it the “Invisible Meal” because of how it interacts with the body’s digestive system, and if it works as well in humans as it already has in mice, the future of weight loss could see serious turnarounds.

Recently published in an issue of Nature Medicine, the findings hinge on a receptor nestled in much of the body’s gut, called the farensoid X receptor, or FXR. It turns on when we begin to eat food, helping bile to digest the contents for nutrient absorption. But where previous weight loss pills have failed, due to harmful scattershot FXR targeting or other means, such as outright appetite suppression, researchers believe the new pill’s mechanism avoids these risks.
"This pill is like an imaginary meal," said Ronald Evans, director of Salk's Gene Expression Laboratory and senior author of the new paper, in a statement. "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."

The pill isn’t for people with just a little extra around the waist, however. It’s intended for the some 29.1 million people who suffer from diabetes, many of whom make up the 78.6 million people, or one-third of the population, who is currently obese. If scientists can perfect the pill’s effectiveness while minimizing side effects, they hope it can someday replace gastric bypass surgery as a desired means of major weight loss.

If mouse models are anything to go by, the future is promising. Over a five-week period, lab mice who took a daily pill of fexaramine, a compound the team developed from the normal drug combination, showed significant weight loss; drops in blood pressure, cholesterol, and blood sugar; and rises in body temperature, which signaled accelerated metabolisms. They also lost significantly more body fat compared to the mice that weren’t on the regimen, and some of the white fat turned to the healthier brown fat that helps burn energy. Why the fexaramine compound works better than the drugs that target FXR in much the same way may have to do with some well-time molecular signaling, the team suggests. "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," Evans said. "We've learned how to trigger the first runner so that the rest of the events happen in a natural order."
Unlike other FXR-targeting drugs, or others of a different kind altogether, the new pill simulates eating an “invisible meal” just in the intestines, not the entire bloodstream. This narrowed focus allows the intestines to receive the full brunt of the pill’s effects, without any hazardous collateral damage incurred by other organs or causing the person to gain weight.
In future trials, Evans and the team hope to transition the findings from mouse to human models. And to allay any remaining naysayers, the pill wouldn’t be a silver bullet for obesity and diabetes; patients would still need to maintain a healthy balance of diet and exercise — something that hopefully will only get easier as the pounds come off.
Source: Fang S, Suh J, Reilly S, et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nature Medicine. 2015.

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