Alterations in intestinal fatty acid metabolism in inflammatory bowel disease
Alterations in intestinal fatty acid metabolism in inflammatory bowel disease
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DOI：
10.1016/j.bbadis.2005.12.006
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发表时间：
2006-03-01
影响因子：
6.2
通讯作者：
Schmitz, G
中科院分区：
文献类型：
--
作者：
Heimerl, S;Moehle, C;Schmitz, G
炎症性肠病（IBD）是发达国家的一种严重肠道疾病，在全球范围内发病率不断增加。即将到来的证据表明肠上皮屏障功能在IBD的发展中起重要作用。脂肪酸对肠细胞具有营养和保护作用，作为转录激活剂，并构成炎症介质的前体。本研究的目的是研究IBD中脂肪酸摄取和内源性脂肪酸生物合成相关基因的差异调节。对来自肠的非受影响区域的粘液组织活检标本进行DNA微阵列分析。基因阵列分析揭示了多种参与脂肪酸摄取和合成的基因在选定的IBD患者的回肠和结肠中差异表达。为了验证这些结果，在较大IBD样品数量中对所选择的调节候选基因进行实时RT-PCR。单次活检结果显示，IBD患者长链酰基辅酶A合成酶（ACSL）1和4表达上调（P < 0.05），而溃疡性结肠炎患者回肠和结肠中脂肪酸合成酶表达显著降低（P < 0.001）。转录因子肝X受体（LXR）的表达，这是以前显示，诱导脂肪酸合成酶基因的表达，在IBD的mRNA水平上没有改变。然而，在使用人肠细胞系LS 174 T的细胞培养实验中，LXR配体T0901317对脂肪酸合酶的诱导被TNF α抑制。此外，这些实验表明TNF α处理降低了LXR蛋白水平。这些数据表明，溃疡性结肠炎患者中脂肪酸合成酶表达的降低可能至少部分是由于在促炎细胞因子存在下LXR表达和功能的丧失。观察到的脂肪酸代谢基因表达的改变可能有助于溃疡性结肠炎的病理生理学。(c)2005 Elsevier B. V.保留所有权利。
Inflammatory bowel disease (IBD) constitutes a severe intestinal disorder in developed countries with increasing incidence worldwide. Upcoming evidence indicates an important role of intestinal epithelial barrier function in the development of IBD. Fatty acids exert nutritional and protective effects on enterocytes, serve as activators of transcription and constitute precursors of inflammatory mediators. The aim of this study was to investigate differential regulation of genes involved in fatty acid uptake and endogenous fatty acid biosynthesis in IBD. Mucosal biopsy specimens from non-affected regions of the intestine were subjected to DNA microarray analysis. Gene array analysis revealed a variety of genes involved in fatty acid uptake and synthesis to be differentially expressed in ileum and colon of selected IBD patients. To verify these results, realtime RT-PCR was performed for selected regulated candidate genes in larger IBD sample numbers. In single biopsy analysis long chain acyl-CoA synthetase (ACSL) 1 and 4 were upregulated in IBD (P < 0.05), while a significant decrease in fatty acid synthase expression was found in ileum and colon of ulcerative colitis patients (P < 0.001). Expression of the transcription factor liver X receptor (LXR) which was previously shown to induce fatty acid synthase gene expression was not altered on mRNA level in IBD. However, in cell culture experiments using the human intestinal cell line LS174T induction of fatty acid synthase by the LXR ligand T0901317 was inhibited by TNF alpha. Moreover, these experiments indicated a decrease of LXR protein levels by TNFa treatment. These data suggest that the decrease of fatty acid synthase expression in ulcerative colitis patients could be at least partially due to a loss of LXR expression and function in the presence of pro-inflammatory cytokines. Observed alterations in expression of genes of fatty acid metabolism may contribute to the pathophysiology of ulcerative colitis. (c) 2005 Elsevier B.V. All rights reserved.