Metabolomics reveals that hepatic stearoyl-CoA desaturase 1 downregulation exacerbates inflammation and acute colitis

被引:149
作者
Chen, Chi [1 ]
Shah, Yatrik M. [1 ]
Morimura, Keiichirou [1 ]
Krausz, Kristopher W. [1 ]
Miyazaki, Makoto [2 ]
Richardson, Terrilyn A. [3 ]
Morgan, Edward T. [3 ]
Ntambi, James M. [2 ]
Idle, Jeffrey R. [4 ]
Gonzalez, Frank J. [1 ]
机构
[1] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] Univ Wisconsin, Dept Biochem & Nutr Sci, Madison, WI 53706 USA
[3] Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA
[4] Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague 12800 2, Czech Republic
关键词
D O I
10.1016/j.cmet.2007.12.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:135 / 147
页数:13
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