Metabolomics Reveals that Hepatic Stearoyl-CoA Desaturase 1 Downregulation Exacerbates Inflammation and Acute Colitis

Chi Chen, Yatrik M. Shah, Keiichirou Morimura, Kristopher W. Krausz, Makoto Miyazaki, Terrilyn A. Richardson, Edward T. Morgan, James M. Ntambi, Jeffrey R. Idle, Frank J. Gonzalez

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

To investigate the pathogenic mechanism of ulcerative colitis, a dextran sulfate sodium (DSS)-induced acute colitis model was examined by serum metabolomic analysis. Higher levels of stearoyl lysophosphatidylcholine and lower levels of oleoyl lysophosphatidylcholine in DSS-treated mice compared to controls led to the identification of DSS-elicited inhibition of stearoyl-CoA desaturase 1 (SCD1) expression in liver. This decrease occurred prior to the symptoms of acute colitis and was well correlated with elevated expression of proinflammatory cytokines. Furthermore, Citrobacter rodentium-induced colitis and lipopolysaccharide treatment also suppressed SCD1 expression in liver. Scd1 null mice were more susceptible to DSS treatment than wild-type mice, while oleic acid feeding and in vivo SCD1 rescue with SCD1 adenovirus alleviated the DSS-induced phenotype. This study reveals that inhibition of SCD1-mediated oleic acid biogenesis exacerbates proinflammatory responses to exogenous challenges, suggesting that SCD1 and its related lipid species may serve as potential targets for intervention or treatment of inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)135-147
Number of pages13
JournalCell Metabolism
Volume7
Issue number2
DOIs
StatePublished - Feb 6 2008
Externally publishedYes

Bibliographical note

Funding Information:
We thank V.I. Zannis for providing adenovirus expressing SCD1 and S. Kimura for control adenovirus. We also appreciate the technical assistance of J. Buckley, U. Jaowattana, and T. Tanabe. J.R.I. is grateful to US Smokeless Tobacco Company for a grant for collaborative research. This study was supported by the NCI Intramural Research Program of the NIH.

Keywords

  • HUMDISEASE
  • SYSBIO

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