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Endotoxin, zymosan, and cytokines decrease the expression of the transcription factor, carbohydrate response element

Kenneth R Feingold1, Judy K Shigenaga, Sophie M Patzek

  • 1Metabolism Section, Department of Veterans Affairs Medical Center, University of California-San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA. kenneth.feingold@ucsf.edu

Innate Immunity
|January 27, 2010
PubMed

Insights

Lipopolysaccharide (LPS) and inflammatory stimuli rapidly decrease carbohydrate response element binding protein (ChREBP) levels in mice. This down-regulation impacts ChREBP target genes, highlighting ChREBP

Area of Science:

  • Metabolism
  • Molecular Biology
  • Immunology

Background:

  • Carbohydrate response element binding protein (ChREBP) regulates glucose metabolism genes.
  • ChREBP activity increases with glucose, promoting lipogenesis.
  • The regulation of ChREBP during inflammatory states is not well understood.

Purpose of the Study:

  • To investigate the effect of inflammatory stimuli on ChREBP expression and activity.
  • To determine if ChREBP is regulated during the acute phase response.
  • To identify tissues where ChREBP expression is affected by inflammation.

Main Methods:

  • Mice were treated with lipopolysaccharide (LPS), zymosan, or turpentine.
  • Hepatic ChREBP mRNA and protein levels were measured.
  • Expression of ChREBP target genes was analyzed.
  • In vitro studies used Hep3B cells treated with TNF-α and IL-1β.

Main Results:

  • LPS treatment caused a rapid and dose-dependent decrease in hepatic ChREBP mRNA and protein.
  • Zymosan and turpentine also reduced liver ChREBP levels and target gene expression.
  • Pro-inflammatory cytokines TNF-α and IL-1β decreased ChREBP expression in vivo and in vitro.
  • ChREBP expression was also reduced in muscle and adipose tissue following LPS treatment.

Conclusions:

  • ChREBP is significantly down-regulated during the acute phase response induced by inflammatory stimuli.
  • This down-regulation affects the expression of key metabolic genes regulated by ChREBP.
  • ChREBP is identified as a transcription factor regulated during acute inflammation.

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