A hormone that helps regulate energy balance in the body also plays an important role in how the body responds to influenza, according to a new study led by researchers at UT Southwestern Medical Center.
The study, published in the Proceedings of the National Academy of Sciences, highlights the potential of this hormone, fibroblast growth factor 21 (FGF21), as a target for new treatments for the flu.
FGF21, known for its role in regulating metabolism and energy balance, was found to rise in both humans and mice during flu infections.
The hormone works by triggering protective responses in the brain to help the body cope with the physiological stress of the infection.
According to senior author Steven Kliewer, Ph.D., a professor of Molecular Biology and Pharmacology at UT Southwestern, “Our work demonstrates that FGF21 acts on the brain to protect against the hypothermia and weight loss caused by influenza infection.”
The study found that FGF21 activates a brain region that helps regulate body temperature by prompting heat production in tissues responsible for thermoregulation.
This thermogenic response helps stabilize body temperature and improves the body’s overall ability to fight off the flu infection. In mice lacking FGF21 or its receptor, recovery was slower, suggesting that FGF21 plays an essential role in the body’s response to flu infection.
Interestingly, while FGF21 helped improve recovery from flu infection, it did not affect viral levels, indicating that its benefits come from reducing the stress caused by the infection rather than directly attacking the virus. The results suggest that FGF21 could help the body respond to a range of infections, not just the flu.
Dr. Kliewer explained, “For serious cases of influenza infection, the care is mostly supportive. Our findings suggest a new pharmacological approach for treating the flu. Further studies are required to determine if these findings are applicable to other infections.”
This research builds on decades of work at UT Southwestern’s Mangelsdorf/Kliewer Lab, where FGF21 was first identified as a hormone produced by the liver in response to metabolic stresses like fasting and alcohol consumption. The new study extends this work by showing that FGF21 can also help the body maintain metabolic balance during illness.
“The immune system is not the only critical part of the response to infection,” said corresponding author Kartik Rajagopalan, M.D., Ph.D., assistant professor of Internal Medicine at UT Southwestern. “There are signals sent to the brain that reprogram metabolism for an optimal response to illness.”
The study represents a collaboration between several departments at UT Southwestern, including Pharmacology, Molecular Biology, and Internal Medicine. The research team also incorporated human data showing that FGF21 levels rise during influenza infection.
“This project highlights the power of integrating basic and clinical research,” said Dr. Kliewer. “There are very few places where a project like this could have blossomed. We’re fortunate that UT Southwestern is one of them.”
This research suggests a new avenue for flu treatment by targeting the body’s metabolic response to infection rather than focusing solely on attacking the virus itself. If future studies confirm these findings, FGF21 could become a novel therapeutic target for treating influenza and potentially other infections as well.
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