Metabolomics reveals that hepatic stearoyl-CoA desaturase 1 downregulation exacerbates inflammation and acute colitis.
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| 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.
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| Authors | 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 |
| Journal | Cell metabolism (Cell Metab) Vol. 7 Issue 2 Pg. 135-47 (Feb 2008) ISSN: 1550-4131 [Print] United States |
| PMID | 18249173 (Publication Type: Journal Article, Research Support, N.I.H., Intramural) |
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