Arcuate nucleus proopiomelanocortin neurons mediate the acute anorectic actions of leukemia inhibitory factor via gp130

Aaron J. Grossberg, Jarrad M. Scarlett, Xinxia Zhu, Darren D. Bowe, Ayesha K. Batra, Theodore P. Braun, Daniel L. Marks

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The proinflammatory cytokine leukemia inhibitory factor (LIF) is induced in disease statesandisknown to inhibit food intake when administered centrally. However, the neural pathways underlying this effect are not well understood. We demonstrate that LIF acutely inhibits food intake by directly activating pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. We show that arcuate POMC neurons express the LIF-R, and that LIF stimulates the release of the anorexigenic peptide, α-MSH from ex vivo hypothalami. Transgenic mice lacking gp130, the signal transducing subunit of the LIF-R complex, specifically inPOMCneurons fail to respond to LIF. Furthermore, LIF does not stimulate the release of α-MSHfrom the transgenic hypothalamic explants. These findings indicate that POMC neurons mediate the acute anorectic actions of central LIF administration and provide a mechanistic link between inflammation and food intake.

Original languageEnglish (US)
Pages (from-to)606-616
Number of pages11
JournalEndocrinology
Volume151
Issue number2
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Endocrinology

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