University of Oklahoma Researchers Discover Hormone That May Reverse Obesity

Researchers at the University of Oklahoma have identified a naturally occurring hormone that shows promising potential in reversing obesity, according to a new study published in the journal Cell Reports.

The hormone, known as FGF21 (fibroblast growth factor 21), appears to target the same brain region involved in metabolism and appetite regulation as popular GLP-1 weight loss medications such as Ozempic and Wegovy, though through different mechanisms.

Lead study author Matthew Potthoff, PhD, a professor of biochemistry and physiology at OU College of Medicine and deputy director of the OU Health Harold Hamm Diabetes Center, described how the research revealed unexpected findings about where in the brain FGF21 sends its signals.

“In our previous studies, we found that FGF21 signals to the brain instead of the liver, but we didn’t know where in the brain,” Potthoff explained. “We thought we would find that it signaled to the hypothalamus, which is widely implicated in body weight regulation, so we were very surprised to discover that the signal was to the hindbrain, which is where the GLP-1 analogs are believed to act.”

The discovery is particularly significant as FGF21 is already involved in the development of a drug to treat metabolic dysfunction-associated steatohepatitis (MASH), a form of fatty liver disease. This creates the possibility for a dual-purpose treatment addressing both obesity and liver disease.

While GLP-1 drugs primarily work by reducing food intake through appetite suppression, FGF21 operates differently—increasing metabolic rate to burn more energy and trigger weight loss. This distinction could potentially lead to new combination therapies or alternatives for patients who don’t respond well to current weight loss medications.

“We hope that by identifying the specific circuit, it can help in the creation of more targeted therapies that are effective without negative side effects,” Potthoff said. The brain circuit that mediates FGF21’s metabolic benefits has also been linked to side effects like gastrointestinal issues and potential bone loss—concerns that would need to be addressed in any human applications.

Dr. Peter Balazs, a hormone and weight loss specialist practicing in New York and New Jersey who wasn’t involved in the research, offered a cautiously optimistic perspective on the findings.

“This discovery raises the possibility of targeting metabolic rate directly, rather than relying only on calorie restriction,” Balazs told Fox News Digital. “However, this is a preclinical mouse study using diet-induced obesity models, which is not fully relevant or similar to human obesity’s chronic metabolic adaptations.”

Balazs highlighted important differences between how FGF21 behaves in humans versus mice. “Obese people actually have higher levels of the hormone in their blood,” he noted, raising questions about how effective FGF21-based treatments would ultimately be in humans.

Early human trials of FGF21 have shown “modest weight loss” between 5% and 8%, according to Balazs—less impressive than the average 15% weight loss seen with GLP-1 treatments. Additionally, it remains unclear whether the body might develop tolerance to FGF21 over time, potentially reducing its effectiveness with long-term use.

Clinical concerns about side effects also persist. “There are important clinical concerns, such as whether FGF21 analogs can cause side effects like digestive issues and bone loss, which is especially risky since obesity already increases the chance of fractures,” Balazs cautioned.

Despite these challenges, Potthoff remains hopeful about developing a new FGF21 drug that could simultaneously target weight loss and MASH, though he acknowledges that additional studies are necessary to explore this potential.

“The study is a nice first step toward alternative biochemical pathways for treating obesity,” Balazs concluded. “However, clinical adoption will require safety trials that include bone density monitoring, along with confirmatory data in humans.”

As obesity rates continue to climb worldwide and demand for weight loss medications outstrips supply, the discovery of alternative pathways and treatments represents an important advancement in metabolic research, potentially broadening the range of options available to patients in the future.