Metabolomics reveals that hepatic stearoyl-CoA desaturase 1 downregulation exacerbates inflammation and acute colitis
Metabolomics reveals that hepatic stearoyl-CoA desaturase 1 downregulation exacerbates inflammation and acute colitis
复制标题
DOI：
10.1016/j.cmet.2007.12.003
复制
发表时间：
2008-02-01
期刊：
影响因子：
29
通讯作者：
Gonzalez, Frank J.
中科院分区：
文献类型：
--
作者：
Chen, Chi;Shah, Yatrik M.;Gonzalez, Frank J.
为探讨溃疡性结肠炎的发病机制，采用血清代谢组学方法建立了葡聚糖硫酸钠(DSS)诱导的大鼠急性结肠炎模型。与对照组相比，DSS处理组小鼠体内较高水平的硬脂酰化溶血磷脂酰胆碱和较低水平的油酰化溶血磷脂酰胆碱导致了DSS对肝脏中硬脂酰辅酶A去饱和酶1(SCD1)表达的抑制。这种下降发生在急性结肠炎症状之前，并与促炎细胞因子的表达升高有很好的相关性。此外，罗氏柠檬酸杆菌诱导的结肠炎和脂多糖治疗也抑制了肝脏中SCD1的表达。SCD1基因缺失的小鼠比野生型小鼠对DSS更敏感，而油酸喂养和SCD1腺病毒体内挽救SCD1腺病毒可减轻DSS诱导的表型。本研究表明，抑制SCD1介导的油酸生物合成加剧了对外源性刺激的促炎反应，提示SCD1及其相关的脂类物种可能成为干预或治疗炎症性疾病的潜在靶点。
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.