Metabolic Hormone FGF21 Shows Surprising Potential to Boost the Body’s Resilience During Flu Infections
A new study has uncovered a fascinating connection between the metabolic hormone FGF21 and how the body handles influenza. Instead of attacking the virus directly, this hormone helps the body tolerate the stress caused by infection. The discovery comes from researchers at UT Southwestern Medical Center and was recently published in the journal Proceedings of the National Academy of Sciences.
This research is packed with specifics about how FGF21 behaves during flu infection, how it interacts with the brain, and why it could open the door to a completely new class of flu treatments. Here is a clear and direct walkthrough of everything the study reveals, along with additional helpful context about this unique hormone.
How FGF21 Responds During a Flu Infection
The study shows that the hormone Fibroblast Growth Factor 21 (FGF21) rises significantly during influenza infection — in both humans and mice. FGF21 is widely recognized for regulating energy balance, especially during periods of metabolic stress such as fasting, extreme cold, or even alcohol exposure. What’s new here is that the hormone also increases in response to infection, suggesting it plays a broader role in helping the body adapt to difficult conditions.
In mice, elevated FGF21 activated a part of the brain involved in controlling the noradrenergic nervous system. This system is closely tied to arousal, metabolism, and temperature regulation. Once activated, it triggered thermogenesis, a process where certain tissues generate heat to stabilize body temperature. Maintaining body temperature is crucial during flu infection, since hypothermia can worsen outcomes and delay recovery.
The research team closely observed what happened when FGF21 was missing from the equation. Mice that lacked FGF21—or lacked the receptor needed to respond to it—experienced more severe hypothermia, worse weight loss, and a slower recovery overall. On the other hand, when mice infected with influenza received pharmacological FGF21, their resilience improved noticeably. They were better able to maintain a stable body temperature and showed milder symptoms.
One of the most significant findings is that FGF21 did not reduce influenza viral levels. The hormone isn’t working like an antiviral drug. Instead, it helps the body withstand the physiological stress caused by the infection. This makes FGF21 part of a class of mechanisms known as disease tolerance pathways, which reduce harm without attacking pathogens directly.
Why This Discovery Matters for Flu Treatment
Most treatments for serious influenza cases are supportive—that means doctors focus on severe symptoms such as dehydration, fever, and respiratory distress rather than eliminating the virus. Antiviral medications like oseltamivir exist, but their effectiveness can vary depending on when symptoms started and which flu strain is involved.
The identification of FGF21 as a stress-buffering hormone opens a new possibility: strengthening the body’s ability to cope with infection. By reinforcing the body’s metabolic stability, a treatment built around FGF21 or its signaling pathway could help:
- prevent dangerous declines in body temperature
- reduce infection-related weight loss
- support energy regulation during illness
- improve overall resilience in severe cases
This approach could eventually be used alongside existing antivirals. It might even help with other infections beyond influenza if future research confirms that FGF21 responds similarly to different pathogens.
The Liver-to-Brain Signaling Pathway Behind FGF21
FGF21 has been the subject of decades of research, especially by the Mangelsdorf/Kliewer Lab at UT Southwestern. Prior studies showed that the hormone is produced by the liver in response to metabolic challenges. It then sends signals to the brain through a circuit that includes the co-receptor beta-Klotho (KLB).
The new research expands on that earlier work by showing that the same liver-to-brain pathway becomes active during infection. It’s a demonstration that the body doesn’t rely solely on the immune system to fight illness. There are other protective systems, like metabolic and neural regulation, that help keep the body stable enough to recover.
Collaborations and Research Approach
This study was the result of close collaboration between multiple departments at UT Southwestern, including:
- Department of Pharmacology
- Department of Molecular Biology
- Department of Internal Medicine
The project also included contributions from postdoctoral researchers, clinical fellows, and human data specialists. Notably, the team analyzed real human samples showing that FGF21 levels rise during natural flu infections.
The lead researchers emphasize that UT Southwestern’s environment—combining clinical and basic science expertise—made this work possible. Their goal is now to explore whether FGF21’s protective effect applies to other infections and to determine how this pathway can be safely targeted in therapies.
What We Know About FGF21 Beyond Flu
To understand why this discovery is important, it helps to look at what FGF21 already does in the body. Here’s a straightforward breakdown of what’s known:
FGF21 Is a Key Metabolic Stress Hormone
When the body experiences stress such as fasting, cold exposure, or nutrient imbalance, FGF21 levels rise. It helps shift metabolism toward survival mode by:
- promoting fat burning
- improving insulin sensitivity
- regulating glucose levels
- influencing energy expenditure
FGF21 Interacts With the Nervous System
The hormone’s effects depend heavily on signaling to brain regions that control metabolism and temperature. It requires the co-receptor KLB and specific neurons to function properly.
There Are Synthetic Versions in Development
Because natural FGF21 breaks down quickly in the bloodstream, biotech companies have been developing long-acting FGF21 analogues. These analogues have primarily been tested for obesity, diabetes, and fatty liver disease. The new findings might expand their potential uses.
FGF21 May Have Effects on Behavior and Circadian Rhythms
Some studies show that FGF21 can influence sleep cycles, physical activity, and even food preferences. This demonstrates how deeply metabolic signals intertwine with neural circuits.
What Comes Next?
The researchers emphasize that more studies are needed, especially on:
- how this pathway functions in humans during illness
- whether FGF21 helps with infections beyond influenza
- what dosage and timing would be necessary for therapeutic use
- how to avoid possible side effects, since FGF21 influences many metabolic systems
Even though the hormone doesn’t lower viral levels, the idea of boosting the body’s ability to tolerate infection could offer a new direction in treating not just flu but a broader set of diseases.
This discovery is one more example of how interconnected the immune system, metabolism, and brain truly are. Understanding these connections may lead to innovative treatments that strengthen the body’s natural resilience when traditional antiviral methods are not enough.
