A hormone seen as a popular target to develop weight-loss drugs works by directly targeting the brain and triggering previously unknown activity in the nervous system, researchers have found.

The fibroblast growth factor 21 (FGF21) hormone has been a key target for developing weight-loss drugs because the protein increases energy expenditure, causing the body to burn calories.

But how the hormone worked was not known until now.

The team at University of Texas’ Southwestern Medical Center discovered that FGF21 acts directly on the brain, activating another hormone called corticotropin-releasing factor (CRF).

CRF then stimulates the nervous system, activating brown adipose tissue which generates body heat by burning fat.

“FGF21 is known for playing a role in weight loss. We had previously shown that the hormone can act directly on the brain in mice to influence functions like reproduction. In the new study, we show that FGF21 also acts directly on the brain to regulate obesity,” said Steven Kliewer, professor of molecular biology and pharmacology.

Specifically, researchers found that the FGF21-CRF pathway activates a part of the nervous system that controls various involuntary body functions, called the sympathetic nervous system, to signal to brown fat.

Brown fat is often considered the “good” fat that actually burns energy by generating heat – called thermogenesis – to protect from the cold.

Once brown fat receives a “weight loss” signal, the tissue burns fat.

“The findings are important to ongoing efforts to understand obesity at a molecular level and thus better respond to the obesity epidemic,” researchers concluded.

The findings were published in the journal Cell Metabolism.