Hormone that Regulates Body Weight may also Work within CNS to Ward off Sepsis

Signaling of the hormone leptin, which is involved in body weight regulation, increases survival during sepsis, according to new research from the University of Cincinnati.

The hormone leptin, involved in body weight regulation, may also work within the central nervous system (CNS) to aid the immune system in warding off sepsis, according to new research from the University of Cincinnati, led by Matthias Tschöp, MD.

Previous research has shown that obesity causes an overproduction of leptin, and that mice that became obese so through diet changes exhibited a “survival advantage” when it came to sepsis. Because of this earlier finding, Tschöp and his research team set out to understand the relationship between leptin and sepsis.

Using leptin-deficient mouse models, including one that was missing leptin receptors everywhere except the CNS, the researchers found that leptin mediates actions in the CNS, in addition to acting directly on immune cells. Leptin replacement therapy was shown to improve the host’s response to a standard model of sepsis.

According to the researchers, leptin-dependent neurocircuitry is required for the immune system to respond properly to sepsis, and damage to this circuitry, or even leptin deficiency, may increase one’s risk of death from sepsis.

"Human congenital leptin deficiency is rare with less than a few dozen patients reported worldwide to date,” the researchers said. “But there is a stunning number of recorded cases of death due to sepsis in this patient population.”

The team hopes that this will help the scientific community develop therapeutic targets for treating infection in people with damaged leptin-dependent neurocircuitry.

Writing in the Journal of Neuroscience, the researchers reported that leptin “signaling in the brain increases survival during sepsis in leptin-deficient as well as in wild-type mice and that endogenous CNS leptin action is required for an adequate systemic immune response. These findings reveal the existence of a relevant neuroendocrine control of systemic immune defense and suggest a possible therapeutic potential for leptin analogs in infectious disease.”