Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a

Seung Soon Im, Leyla Yousef, Christoph Blaschitz, Janet Z. Liu, Robert A. Edwards, Stephen G. Young, Manuela Raffatellu, Timothy F. Osborne

Research output: Contribution to journalArticle

Abstract

We show that mice with a targeted deficiency in the gene encoding the lipogenic transcription factor SREBP-1a are resistant to endotoxic shock and systemic inflammatory response syndrome induced by cecal ligation and puncture (CLP). When macrophages from the mutant mice were challenged with bacterial lipopolysaccharide, they failed to activate lipogenesis as well as two hallmark inflammasome functions, activation of caspase-1 and secretion of IL-1β. We show that SREBP-1a activates not only genes required for lipogenesis in macrophages but also the gene encoding Nlrp1a, which is a core inflammasome component. Thus, SREBP-1a links lipid metabolism to the innate immune response, which supports our hypothesis that SREBPs evolved to regulate cellular reactions to external challenges that range from nutrient limitation and hypoxia to toxins and pathogens.

Original languageEnglish (US)
Pages (from-to)540-549
Number of pages10
JournalCell Metabolism
Volume13
Issue number5
DOIs
StatePublished - May 4 2011
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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