Genome-wide analysis of PPARα activation in murine small intestine
Genome-wide analysis of PPARα activation in murine small intestine
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DOI：
10.1152/physiolgenomics.00198.2006
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发表时间：
2007-07-18
影响因子：
4.6
通讯作者：
Muller, Michael
中科院分区：
文献类型：
--
作者：
Bunger, Meike;van den Bosch, Heleen M.;Muller, Michael
过氧化物酶体增殖物激活受体α (PPAR α)是一种脂肪酸激活的转录因子，它控制着多种生物过程。人们对PPAR α在小肠中的作用知之甚少。由于这个器官经常通过饮食暴露于高水平的PPAR α配体，我们开始使用功能基因组学实验和生物信息学工具来表征PPAR α在小肠中的功能。PPAR α在人和鼠小肠中均有高水平表达。详细分析表明，PPAR α在空肠近端绒毛细胞中表达量最高。对所有组织样本的芯片分析显示，除了参与脂肪酸和甘油三酯代谢的基因外，与甾醇和胆汁酸代谢相关的转录因子和酶，包括FXR和SREBP1，也被特异性诱导。相反，参与细胞周期和分化、细胞凋亡和宿主防御的基因被PPAR α激活抑制。进一步的分析表明肠道PPAR α依赖基因调控发生在绒毛细胞中。形态学数据证实了阵列结果的功能含义。WY14643对野生型小鼠的绒毛高度和绒毛面积分别增加了22%和34%。这是第一份全面概述小肠中PPAR α控制过程的报告。我们发现PPAR α在小肠中是一个重要的转录调节因子，这可能对开发新型食物和治疗肥胖和炎症性肠病具有重要意义。
The peroxisome proliferator- activated receptor alpha ( PPAR alpha) is a fatty acid-activated transcription factor that governs a variety of biological processes. Little is known about the role of PPAR alpha in the small intestine. Since this organ is frequently exposed to high levels of PPAR alpha ligands via the diet, we set out to characterize the function of PPAR alpha in small intestine using functional genomics experiments and bioinformatics tools. PPAR alpha was expressed at high levels in both human and murine small intestine. Detailed analyses showed that PPAR alpha was expressed most highly in villus cells of proximal jejunum. Microarray analyses of total tissue samples revealed, that in addition to genes involved in fatty acid and triacylglycerol metabolism, transcription factors and enzymes connected to sterol and bile acid metabolism, including FXR and SREBP1, were specifically induced. In contrast, genes involved in cell cycle and differentiation, apoptosis, and host defense were repressed by PPAR alpha activation. Additional analyses showed that intestinal PPAR alpha- dependent gene regulation occurred in villus cells. Functional implications of array results were corroborated by morphometric data. The repression of genes involved in proliferation and apoptosis was accompanied by a 22% increase in villus height and a 34% increase in villus area of wild- type animals treated with WY14643. This is the first report providing a comprehensive overview of processes under control of PPAR alpha in the small intestine. We show that PPAR alpha is an important transcriptional regulator in small intestine, which may be of importance for the development of novel foods and therapies for obesity and inflammatory bowel diseases.