Better Fat Loss Therapies for Humans: Eat More and Weigh Less

Want to eat more and weigh less? It turns out that there may just be a way to accomplish this seemingly impossible feat. Scientists have discovered key details of a brain-to-body signaling circuit that enables roundworms to lose weight independently of food intake, which could lead to future therapies in humans.

In order to better understand the science of weight loss, researchers examined the weight loss circuitry of C. elegans, the roundworm. Serotonin signaling, which can be increased artificially by some diet and antidepressant drugs, has long been known to reduce weight. Until recently, though, scientists thought that it does so largely by suppressing appetite and food intake. Yet in 2008, researchers found that serotonin changes food intake and fat levels via separate signaling pathways. Needless to say, they wanted to look a bit closer at what might cause this fat loss.

The scientists used a series of gene-blocking experiments to identify some of the roundworm's weight loss circuit's key elements. They found that serotonin actually isn't the sole driver of this weight-loss pathway. Instead, it works in concert with another neurotransmitter, octopamine. This neurotransmitter is the roundworm's version of adrenaline in mammals.

That's not all the researchers found, though. They also mapped out a self-reinforcing network of serotonin and octopamine-producing neurons in the worms that send the lose-weight signal to the body. This network included a set of serotonin-sensitive neurons known as URX neurons. These have access to the worm circulatory system and apparently release a signaling molecule that scientists have yet to identify. The result of this signal is a boost in the production of a key enzyme which cuts fat molecules in a way that leads to their further metabolic breakdown.

The findings reveal a little bit more about weight loss. More interesting, though, is that human experience with weight-loss drugs already hints that mammals may have a similar fat-loss circuit. This could mean that there may be new treatments in the future that could help promote weight loss in humans.

"We wonder if boosting not just serotonin but serotonin plus a little bit of adrenaline is the real key to more potent weight loss," said Supriya Srinivasan, one of the researchers, in a news release.

The findings are published in the journal Cell Metabolism.