CNS leptin action modulates immune response and survival in sepsis

Johannes Tschöp, Ruben Nogueiras, Sarah Haas-Lockie, Kevin R. Kasten, Tamara R. Castañeda, Nadine Huber, Kelsey Guanciale, Diego Perez-Tilve, Kirk Habegger, Nickki Ottaway, Stephen C. Woods, Brian Oldfield, Iain Clarke, Chua Streamson, I. Sadaf Farooqi, Stephen O'Rahilly, Charles C. Caldwell, Matthias H. Tschöp

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Sepsis describes a complex clinical syndrome that results from an infection, setting off a cascade of systemic inflammatory responses that can lead to multiple organ failure and death. Leptin is a 16 kDa adipokine that, among its multiple known effects, is involved in regulating immune function. Here we demonstrate that leptin deficiency in ob/ob mice leads to higher mortality and more severe organ damage in a standard model of sepsis in mice [cecal ligation and puncture (CLP)]. Moreover, systemic leptin replacement improved the immune response to CLP. Based on the molecular mechanisms of leptin regulation of energy metabolism and reproductive function, we hypothesized that leptin acts in the CNS to efficiently coordinate peripheral immune defense in sepsis.Wenow report 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.

Original languageEnglish (US)
Pages (from-to)6036-6047
Number of pages12
JournalJournal of Neuroscience
Volume30
Issue number17
DOIs
Publication statusPublished - Apr 28 2010

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Tschöp, J., Nogueiras, R., Haas-Lockie, S., Kasten, K. R., Castañeda, T. R., Huber, N., ... Tschöp, M. H. (2010). CNS leptin action modulates immune response and survival in sepsis. Journal of Neuroscience, 30(17), 6036-6047. https://doi.org/10.1523/JNEUROSCI.4875-09.2010