This Metabolism-Boosting Hormone May Help You Live Longer

Humans aren’t alone when it comes to the consequences of a high-fat diet. In fact, mice deal with some of the same outcomes that humans do when they overconsume fatty foods, from obesity to metabolic dysfunction, to heart disease and diabetes. However, mice at the University of Texas Southwestern Medical Center have helped researchers identify a possible solution to these outcomes — a solution that resides within the fat cells of humans and mice alike.

Revealing their results in a new study in Cell Metabolism, the researchers found that the overproduction of a certain hormone called Fibroblast Growth Factor 21, or FGF21 for short, led to healthier metabolisms and longer lives in adult mice that had been fed a diet of high-fat food. According to the team, this hormone — which is produced by an assortment of body tissues, including fat cells themselves — could contribute to a host of new treatments that could have similar outcomes for the metabolisms and lifespans of humans.

“This is the first long-term aging study to demonstrate the powerful protective effects that FGF21 exerts through fat tissue,” said Philipp Scherer, a study author and professor of internal medicine at UT Southwestern, according to a press release.

Read More: Fat Cells Can Retain a Genetic Memory — Even After Weight Loss

Revisiting the ‘Starvation Hormone’

In a study in eLife published around a decade ago, UT Southwestern researchers determined that the overproduction of FGF21 improved metabolisms and extended lifespans in mice. Dubbing it the “starvation hormone,” they described FGF21 as a driver of some of the positive aspects of “the adaptive starvation response,” which were promoted without a reduction in the mice’s food intake.

The results were mice with increased insulin sensitivities — a standard marker of metabolic health — and increased longevities, which were expanded by around 30 to 40 percent. But the exact mechanisms through which FGF21 generated these effects were unclear. Were the benefits dependent on the location or the timing of the hormone’s overproduction? Were they dependent on the diet of the mice?

These initial researchers arrived at their results by genetically altering their mice’s liver cells to overproduce FGF21 from birth, which meant that the team was unable to determine how the overproduction would affect mice if the hormone was overproduced elsewhere (such as in fat cells) or later on in life. Moreover, the hormone’s production was induced in mice that hadn’t consumed a high-fat diet, meaning their tests weren’t able to account for the hormone’s effects on those with an appetite for fatty foods.

Finding Future Potential in FGF21

To tease out some of these unknowns, the authors of the new study tinkered with their mice’s fat cells to ensure that they would overproduce FGF21 starting only in adulthood. They also fed their mice a high-fat diet and continued this diet throughout the course of their tests.

“We found that FGF21 lowers harmful lipids called ceramides, particularly in visceral fat, which are closely linked to heart disease and diabetes. These findings support FGF21 as a promising target for treating or preventing diseases such as Type 2 diabetes, cardiovascular disease, fatty liver disease, and kidney disease,” Scherer said in the release.

According to the UT Southwestern team, the mice with the genetically altered fat cells showed increased insulin sensitivity and lifespans. They also showed reduced weight gain without alterations to their diets and other signs of healthy aging, like lower levels of inflammatory immune cells.

Ultimately, while more research is required to reveal the possible effects of an overproduction of the hormone on humans, the results show promising signs for FGF21’s future as a tool for human health intervention. Indeed, the genetically altered mice lived for an average of 2.2 years, or 0.4 years longer than the genetically unaltered mice, and for a maximum of 3.3 years, which is comparable to a long, healthy human lifespan.

“By discovering how a naturally occurring hormone protects against chronic disease, we are laying the foundation for future treatments that extend not just lifespan, but also quality of life,” Scherer said in the release.

Read More: Your Fat Cells Never Disappear — Making Future Weight Gain More Likely

Article Sources

Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:

• Cell Metabolism. FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression

• eLife. The Starvation Hormone, Fibroblast Growth Factor-21, Extends Lifespan in Mice

Sam Walters is a journalist covering archaeology, paleontology, ecology, and evolution for Discover, along with an assortment of other topics. Before joining the Discover team as an assistant editor in 2022, Sam studied journalism at Northwestern University in Evanston, Illinois.

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