Natural hormone may reduce obesity without cutting calories, scientists say

Researchers at the University of Oklahoma have discovered a hormone that appears to reverse obesity in the body.

The new study, published in the journal Cell Reports, used mouse models to identify a naturally occurring hormone called FGF21 (fibroblast growth factor 21).

The hormone "appears to work by signaling to a brain region involved in metabolism and appetite regulation, the same area targeted by the popular GLP-1 drugs," according to a university press release.

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FGF21 is reportedly already involved in the development of a drug to treat metabolic dysfunction-associated steatohepatitis (MASH), which is a form of fatty liver disease.

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, said the study showed how the hormone sends "signals" to the lower back region of the brain.

"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," he wrote.

"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."

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The brain circuit behind these metabolic benefits appears to work by "mediating the effects of FGF21," Potthoff said — a process that can also be linked to side effects like gastrointestinal issues and, in some cases, bone loss.

"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," he added.

The FGF21 and GLP-1 hormones act differently, although they target the same area of the brain, according to the researchers. While GLP-1 reduces food intake via appetite, FGF21 increases metabolic rate, burning energy and triggering weight loss.

Potthoff shared his hope for a new FGF21 drug that could target both weight loss and MASH, noting that additional studies are necessary to explore this potential.

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Dr. Peter Balazs MD, a hormone and weight loss specialist practicing in New York and New Jersey, said this discovery raises the possibility of targeting metabolic rate "directly," rather than relying only on calorie restriction.

"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," he told Fox News Digital.

FGF21 behaves differently in humans than in mice, as obese people have higher levels of the hormone in their blood, according to Balazs. This raises the question of how effective FGF21-based treatments would be.

"There are also 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," he cautioned. "The study doesn’t explain how these issues might be managed."

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Early human trials of FGF21 showed "modest weight loss" between 5% and 8%, according to Balazs, which is "less impressive" compared to GLP-1 treatments' average 15% weight loss.

It is also unclear whether the body could develop tolerance to FGF21 over time, which could reduce its effectiveness with long-term use, he added.

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