Worm study could pave way for better fat-loss therapies for humans
Washington: A research led by an Indian origin scientist has revealed that two important neurotransmitters, serotonin and adrenaline, might help develop pharmacological solutions for people who want to burn fat faster.
Scientists discovered key details of a brain-to-body signalling circuit that enables roundworms to lose weight independently of food intake.
The weight-loss circuit is activated by combined signals from the worm versions of the neurotransmitters serotonin and adrenaline, and there are reasons to suspect that it exists in a similar form in humans and other mammals.
The study's lead researcher, Supriya Srinivasan from The Scripps Research Institute said that boosting serotonin signalling has been seen as a viable strategy for weight loss in people, but their results hint that boosting serotonin plus adrenaline should produce more potent effects.
Serotonin signalling, which can be increased artificially by some diet and antidepressant drugs, has long been known to reduce weight. Until recently, scientists assumed that it does so largely by suppressing appetite and food intake.
However, Srinivasan reported in 2008 that serotonin changes food intake and fat levels via separate signalling pathways.
Her experiments were conducted on C. elegans roundworms, whose short lifespans and well-characterized nervous systems make them a preferred species for quick-turnaround lab studies. Indeed, other researchers soon found that serotonin's food-intake-suppressing and weight-loss effects are separable in mammals, too.
In the new study, Srinivasan and her colleagues found that serotonin isn't the sole driver of this weight-loss pathway, but works in concert with another neurotransmitter, octopamine-the C. elegans version of adrenaline in mammals.
The team 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 includes a set of serotonin-sensitive neurons known as URX neurons, which have access to the worm circulatory system and apparently release a still-to-be-identified signaling molecule.
The downstream result of this signal, the researchers found, is a boost in the production of a key enzyme in the worm intestine. The enzyme, known as adipocyte triglyceride lipase 1 (ATGL-1), literally cuts fat molecules in a way that leads to their further metabolic breakdown. ATGL-1 also has a very similar counterpart in mammals.
The study is published in the journal Cell Metabolism.