A hormone called FGF21 can fight obesity in mice by activating a newly identified brain circuit linked to metabolism. The discovery could pave the way to more precise treatments for weight loss and liver disease in humans, reports ScienceDaily, cited by Agerpres.
Researchers at the University of Oklahoma discovered that the hormone works by sending signals to a region of the brain that helps control metabolism and appetite. This is the same general area targeted by GLP-1 class drugs such as Wegovy and Ozempic for weight loss. The findings were published in the scientific journal Cell Reports.
The hormone, known as FGF21, has already attracted attention as a potential target for new therapies. Drugs designed to act on this pathway are currently being tested in clinical trials for metabolic dysfunction-associated steatohepatitis (MASH), a serious form of fatty liver disease.
Lead researcher Dr. Matthew Potthoff and his team focused on understanding exactly how FGF21's effects occur. Their results show that this hormone acts through the hindbrain.
What the researchers say about their discovery
“In our previous studies, we found that FGF21 sends signals to the brain instead of the liver, but we didn't know exactly where in the brain,” said Potthoff, a professor of biochemistry and physiology at the University of Oklahoma School of Medicine and deputy director of the Harold Hamm Diabetes Center at OU Health.
“We thought we would find that it was signaling to the hypothalamus (which is widely involved in body weight regulation), so we were very surprised to find that the signal was going to the hindbrain, where GLP-1 analogs are thought to act,” he explained.
Specifically, FGF21 interacts with two areas of the hindbrain called the nucleus of the solitary tract (NTS) and the area postrema (AP). These regions then communicate with another brain structure known as the parabrachial nucleus. This signaling chain is essential for the hormone's ability to influence metabolism and reduce body weight.
“This brain circuit appears to mediate the effects of FGF21,” Potthoff said. “We hope that identifying the specific circuit can help create more targeted therapies that are effective without side effects. FGF21 analogs have side effects such as gastrointestinal problems and, in some cases, bone loss,” added the researcher.
The hormone acts differently from drugs such as Wegovy and Ozempic
Although FGF21 and GLP-1 treatments target similar areas of the brain, they act in very different ways. GLP-1 drugs reduce appetite and food intake, while FGF21 drugs increase metabolic activity, helping the body burn more energy and lose weight.
Potthoff and his team are confident that this research could lead to new treatments for both obesity and MASH.
“Although this study focused on the mechanism by which FGF21 reduces body weight, further research is needed to determine whether this circuit also mediates the ability of FGF21 and its analogs to reverse MASH,” he stated.
