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Leptin action in the brain linked to sepsis survival
Date:4/30/2010

CINCINNATIThe hormone leptin, typically associated with body weight regulation, works within the central nervous system (CNS) to aid the immune system's defense against sepsis, researchers say.

Sepsis is a life-threatening medical condition in which the entire body is overwhelmed by infection.

A study led by Matthias Tschp, MD, of UC's Metabolic Diseases Institute, and Charles Caldwell, PhD, of UC's surgery department, is the first to describe leptin's role in the control of immune response via the CNS. Results are published this week in the Journal of Neuroscience, the official journal of the Society for Neuroscience.

"Indirect evidence has previously indicated that the central nervous system might have a role in maintaining the immune system," says Tschp. "For example, people with brain injuries appear to be at a higher risk for infection and sepsis. Sepsis is also a serious complication for stroke patients. What was lacking was any molecular mechanism to explain that relationship."

Researchers know that obesity causes an overproduction of leptin. High leptin levels make receptors "deaf" to the hormone, resulting in a loss of leptin function (leptin resistance) that leads to higher food intake.

Diet-induced induced obese mice have a survival advantage in sepsis. Because of this, the team hypothesized that leptin resistance, which is seen at neurons regulating body weight, may not be happening at the brain centers that regulate the immune system.

To prove this, the team studied several leptin-deficient mouse models, including one that was missing leptin receptors everywhere except within the CNS. They report that leptin, long thought to act directly on immune cells themselves, also mediates actions in the CNS. They showed that leptin replacement improved the host response to a standard model of sepsis.

Leptin-dependent neurocircuitry, the authors say, is required for a proper immune
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Contact: Dama Kimmon
dama.kimmon@uc.edu
513-558-4519
University of Cincinnati Academic Health Center
Source:Eurekalert

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Unit Definition: 1 U corresponds to the amount of enzyme which produces 1 mol protons per minute at pH 5.5 and 30C (peptin from citrus peel, Fluka-No. 76280, as substrate)...
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