Scientists have uncovered a critical mechanism in the body’s fat-burning process, offering a profound glimpse into the inner workings of the metabolic process and, perhaps, hope for a new class of fat-busting drugs.
In their breakthrough research, scientists from The Scripps Research Institute monitored the activity of serotonin, a brain hormone long known to regulate appetite and energy balance.
Previous research has shown that “serotonin, a central neuromodulator with ancient ties to feeding and metabolism, is a major driver of body fat loss,” write the researchers in the journal Nature Communications.
But while previous studies had found many links between the brain hormone and energy use, the core question remained: How, exactly, does serotonin impact metabolism?
To find an answer, the researchers launched an innovative experiment using a type of roundworm called C. elegans that features many of the same signaling hormones in the brain as humans.
The researchers embarked on a painstaking process of deleting genes in C. elegans on a one-by-one basis in the hope of disrupting the connection between serotonin and fat burning. Simply put, the researchers were hoping to pinpoint one gene out of the entire C. elegans genotype that, when turned off, would result in a lack of fat burning due to serotonin disruption.
This onerous process led the researchers to a single gene, which they referred to as FLP-7.
“This was basic science that unlocked an interesting mystery,” said lead author Supriya Srinivasan, an Assistant Professor at The Scripps Research Institute.
Tracking the Targeted Gene
After honing in on the promising FLP-7 gene, the researchers set out to discover if the gene led them directly to the serotonin hormone in the brain. They tagged the FLP-7 gene with a red protein, and they were able to track the movement of the gene within the roundworms because of their transparent skin.
What they found was a veritable map of the brain-to-gut metabolic process. Specifically, they discovered that neurons in the brain of C. elegans secreted the FLP-7 gene when faced with high serotonin levels. After the gene was secreted, it moved throughout the body and ended up smack in the middle of the gut, where it began the process of burning fat.
“That was a big moment for us,” said Srinivasan.
The research marks the first time a study has identified a discrete brain hormone that actively engages fat metabolism.
“Our studies presented here uncover a previously undefined neuroendocrine signaling pathway that preferentially stimulates body fat loss,” note the researchers.
The researchers subsequently discovered that when they tinkered with the animals’ FLP-7 levels, rather than adjusting serotonin levels, they found no side effects.
That’s crucial for the potential development of new drugs because prior research that increased or decreased serotonin levels had carried with it a range of dangerous side effects.
“In humans, with respect to the control of energy balance, global serotonergic agonists and antagonists have long been administered to suppress appetite, increase energy expenditure, or both,” write the researchers. “The limited efficacy of these global serotonin-boosting compounds is often accompanied by substantial side effects, and has mitigated their use.”
While the research may ultimately lead to future pharmaceutical interventions, for now the researchers are calling for additional research into adjusting FLP-7 levels and its effect on energy and metabolism.