University of Oklahoma researchers say FGF21 boosted metabolic rate in mouse models, suggesting a possible obesity pathway distinct from appetite suppression.
A naturally occurring hormone may point to a different way to treat obesity: increasing the body’s energy use rather than simply reducing appetite.
Researchers at the University of Oklahoma reported in a Cell Reports study that the hormone FGF21, or fibroblast growth factor 21, appeared to reverse obesity in mouse models by signaling to a brain region involved in metabolism and appetite regulation. That region is also believed to be targeted by popular GLP-1 weight-loss drugs, but the researchers said FGF21 appears to work through a different mechanism.
The finding matters because current obesity drugs that mimic GLP-1 can be highly effective but generally work by reducing food intake. FGF21, by contrast, was described by the researchers as increasing metabolic rate, causing the body to burn more energy and triggering weight loss without the same appetite-centered pathway.
Matthew Potthoff, a professor of biochemistry and physiology at the OU College of Medicine and deputy director of the OU Health Harold Hamm Diabetes Center, said the team had expected FGF21 to act in the hypothalamus, a brain region long associated with weight regulation. Instead, the signal appeared in the hindbrain, the same broad area where GLP-1 analogs are believed to act.
FGF21 is already being studied in connection with metabolic dysfunction-associated steatohepatitis, or MASH, a form of fatty liver disease. Potthoff said additional research is needed to explore whether an FGF21-based drug could eventually address both weight loss and MASH.
The study remains early-stage, and its main evidence comes from diet-induced obesity models in mice. Dr. Peter Balazs, a hormone and weight-loss specialist in New York and New Jersey, told Fox News Digital that the discovery raises the possibility of targeting metabolic rate directly, but cautioned that mouse models do not fully capture the chronic metabolic changes seen in human obesity.
There are also unresolved safety questions. Potthoff noted that the same brain circuit tied to FGF21’s metabolic effects may also be linked to gastrointestinal problems and, in some cases, bone loss. Balazs said those concerns are clinically important, especially because obesity itself can raise fracture risk.
Early human trials of FGF21 have shown modest weight loss of about 5% to 8%, Balazs said, below the roughly 15% average weight loss associated with GLP-1 treatments. He also said it is not yet clear whether the body could develop tolerance to FGF21 over time, potentially weakening long-term results.
“The study is a nice first step toward alternative biochemical pathways for treating obesity,” Balazs said. “However, clinical adoption will require safety trials that include bone density monitoring, along with confirmatory data in humans.”
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