NF-κB activation in hypothalamic pro-opiomelanocortin neurons is essential in illness- and leptin-induced anorexia

Pil Geum Jang, Cherl Namkoong, Gil Myoung Kang, Man Wook Hur, Seung Whan Kim, Geun Hyang Kim, Yeoungsup Kang, Min Jae Jeon, Eun Hee Kim, Myung Shik Lee, Michael Karin, Ja Hyun Baik, Joong Yeol Park, Ki Up Lee, Young Bum Kim, Min Seon Kim

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Anorexia and weight loss are prevalent in infectious diseases. To investigate the molecular mechanisms underlying these phenomena, we established animal models of infection-associated anorexia by administrating bacterial and viral products, lipopolysaccharide (LPS) and human immunodeficiency virus-1 transactivator protein (Tat). In these models, we found that the nuclear factor-κB (NF-κB), a pivotal transcription factor for inflammation-related proteins, was activated in the hypothalamus. In parallel, administration of LPS and Tat increased hypothalamic pro-inflammatory cytokine production, which was abrogated by inhibition of hypothalamic NF-κB. In vitro, NF-κB activation directly stimulated the transcriptional activity of proopiomelanocortin (POMC), a precursor of anorexigenic melanocortin, and mediated the stimulatory effects of LPS, Tat, and pro-inflammatory cytokines on POMC transcription, implying the involvement of NF-κB in controlling feeding behavior. Consistently, hypothalamic injection of LPS and Tat caused a significant reduction in food intake and body weight, which was prevented by blockade of NF-κB and melanocortin. Furthermore, disruption of IκB kinase-β, an upstream kinase of NF-κB, in POMC neurons attenuated LPS- and Tat-induced anorexia. These findings suggest that infection-associated anorexia and weight loss are mediated via NF-κB activation in hypothalamic POMCneurons. In addition, hypothalamic NF-κB was activated by leptin, an important anorexigenic hormone, and mediates leptin-stimulated POMC transcription, indicating that hypothalamic NF-κB also serves as a downstream signaling pathway of leptin.

Original languageEnglish
Pages (from-to)9706-9715
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number13
DOIs
Publication statusPublished - 2010 Mar 26

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'NF-κB activation in hypothalamic pro-opiomelanocortin neurons is essential in illness- and leptin-induced anorexia'. Together they form a unique fingerprint.

Cite this