PNAS: Obese Hormones Increase the Risk of Sepsis

Scientists from the Gulbenkian de Ciência Institute (IGC) led by Luís Moita have discovered that a hormone believed to treat obesity reduces the body’s resistance to bacterial infections and increases the risk of sepsis. The research results were recently published in PNAS.

 

Sepsis is a potentially fatal disease that stems from the dysregulation of the organism’s response to infection, leading to organ failure. A recent study published in the scientific journal “The Lancet” estimated that in 2017 sepsis infected 49 million people and 11 million people died globally. To expand their understanding of the disease, IGC’s Luis Moita’s group investigated whether a hormone called GDF15 (growth and differentiation factor 15) can play a role in sepsis. This hormone has been extensively studied by many laboratories and drugs as a potential drug for the treatment of obesity.

 

 

IGC researchers measured the levels of GDF15 in blood samples from patients with sepsis undergoing treatment in the intensive care unit, and compared these levels with healthy individuals and patients diagnosed with appendicitis. The results showed that GDF15 levels in sepsis patients increased compared with other groups, and high levels of hormones were associated with mortality.

 

The study was conducted in mice lacking the GDF15 gene. The results obtained indicate that mice survive better in bacterial abdominal infections similar to sepsis in human patients, indicating that the hormone plays a role in sepsis. Subsequently, the researchers studied what caused the survival rate of mice without GDF15 to increase. They pointed out that these mice can absorb more white blood cells for the abdomen, especially neutrophils, to better control the infection and prevent it from spreading quickly to other parts of the body.

 

Luís Moita warned: “When many pharmaceutical companies and groups are considering the use of GDF15 as a complementary therapy for obesity, it is important to remember that this treatment strategy may increase the risk of serious infections, including sepsis.”

 

 

Reference

Santos, I., et al. (2020) CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15-deficient mice protects against abdominal sepsis. PNAS. doi.org/10.1073/pnas.1918508117.