Although the neurotransmitter serotonin has previously been shown to play a central role in regulating appetite (amongst other things), the reasons for this remained unclear. In an attempt to shed some light on the subject, biologists at The Scripps Research Institute (TSRI) conducted experiments on C. elegans roundworms and identified a brain hormone that selectively triggers fat burning in the gut, regardless of food intake – and the findings could have implications for humans.
TSRI Assistant Professor Supriya Srinivasan, senior author of the new study, and her colleagues made the discovery through a process of elimination. They started with C. Elegans roundworms, which are commonly used in biology as model organisms because their brains produce many of the same signaling molecules as humans. They then systematically deleted one gene after another in the roundworm in an attempt to identify which gene was responsible for fat burning.
The gene they were looking for turned out to be one that codes for a neuropeptide hormone dubbed FLP-7, the mammalian version of which is called Tachykinin and was, believe it or not, identified 80 years ago as triggering muscle contractions when dribbled on pig intestines. Although scientists at the time believed the hormone connected the brain to the gut, since then no one had made a link between Tachykinin and fat metabolism.
Tagging FLP-7 with a fluorescent red protein to make it visible in the transparent body of the living roundworm, study first author Lavinia Palamiuc showed that in response to elevated serotonin levels, FLP-7 was indeed secreted from neurons in the brain and traveled via the circulatory system to the gut where it triggered the fat-burning process. The researchers were justifiably excited, claiming this was the first time a brain hormone had been identified that specifically and selectively stimulates fat metabolism, without any effect on food intake.
The researchers describe the newly-discovered fat-burning pathway as working like this: in response to sensory cues, such as food availability, serotonin is produced in a neural circuit in the brain, which prompts another set of neurons to produce FLP-7. The FLP-7 then makes its way to the gut where a receptor in intestinal cells is activated that starts the intestines turning fat into energy.
While altering serotonin levels alone can have an impact on movement and reproductive behavior in addition to an animal’s food intake, the researchers haven’t found any obvious side effects to increasing FLP-7 levels further downstream. Instead, the roundworms continued to function normally, while burning more fat. This bodes well for potential future research into how FLP-7 levels could be altered to increase fat burning without any of the side effects associated with the manipulation of serotonin levels.
Although the research involved roundworms, the researchers believe their findings could have implications for future pharmaceutical development for humans.