Inflammation triggers liver X receptor-dependent lipogenesis

Sophie R. Liebergall, Jerry Angdisen, Shun Hang Chan, Ying Ju Chang, Timothy F. Osborne, Alexander F. Koeppel, Stephen D. Turner, Ira G. Schulman

Research output: Contribution to journalArticlepeer-review

Abstract

Immune cell function can be modulated by changes in lipid metabolism. Our studies indicate that cholesterol and fatty acid synthesis increases in macrophages between 12 and 18 h after the activation of Toll-like receptors with proinflammatory stimuli and that the upregulation of lipogenesis may contribute to the resolution of inflammation. The inflammation-dependent increase in lipogenesis requires the induction of the liver X receptors, members of the nuclear receptor superfamily of transcription factors, by type I interferons in response to inflammatory signals. Instead of the well-established role for liver X receptors in stimulating cholesterol efflux, we demonstrate that liver X receptors are necessary for the proper resumption of cholesterol synthesis in response to inflammatory signals. Thus, liver X receptors function as bidirectional regulators of cholesterol homeostasis, driving efflux when cholesterol levels are high and facilitating synthesis in response to inflammatory signals. Liver X receptor activity is also required for the proper shutdown of a subset of type I interferon-stimulated genes as inflammation subsides, placing the receptors in a negative-feedback loop that may contribute to the resolution of the inflammatory response.

Original languageEnglish (US)
Article numbere00364-19
JournalMolecular and cellular biology
Volume40
Issue number2
DOIs
StatePublished - Jan 1 2020

Keywords

  • Inflammation
  • Lipid synthesis
  • Lipids
  • Macrophage
  • Nuclear receptor
  • Transcription
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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