PPARalpha-mediated effects of dietary lipids on intestinal barrier gene expression.
PPARalpha-mediated effects of dietary lipids on intestinal barrier gene expression.
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DOI：
10.1186/1471-2164-9-231
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发表时间：
2008-05-19
期刊：
影响因子：
4.4
通讯作者：
Müller M
中科院分区：
文献类型：
--
作者：
de Vogel-van den Bosch HM;Bünger M;de Groot PJ;Bosch-Vermeulen H;Hooiveld GJ;Müller M
小肠中营养物质和其他食物成分的选择性吸收是由一组转运蛋白和代谢酶介导的，通常统称为“肠屏障蛋白”。介导膳食脂质对基因表达影响的重要受体是过氧化物酶体增殖物激活受体α（PPARα），它在肠上皮细胞中大量表达。在这项研究中，我们研究了 PPARα 的急性营养激活对编码肠道屏障蛋白的基因表达的影响。为此，我们使用由相同脂肪酸组成的三酰甘油并结合野生型和 PPARα 缺失小鼠的基因表达谱。以合成 PPARα 激动剂 WY14643 治疗作为参考。我们鉴定了 74 个屏障基因，这些基因在用 WY14643 激活 6 小时后受到 PPARα 依赖性调节。对于二十碳五烯酸 (EPA)、二十二碳六烯酸 (DHA) 和油酸 (OA)，这些数字分别为 46、41 和 19。 EPA、DHA 和 WY14643 调节基因之间的重叠相当大，而 OA 处理显示出有限的重叠。从我们的数据推断出的功能意义表明，营养激活的 PPARα 调节的转运蛋白和 I/II 相代谢酶参与 a) 脂肪酸氧化，b) 胆固醇、葡萄糖和氨基酸转运和代谢，c) 肠道蠕动，以及 d) 氧化应激防御。我们鉴定了在脂肪酸急性激活后受 PPARα 依赖性调节的肠道屏障基因。这些知识让我们更好地了解膳食脂肪对肠道屏障功能的影响，确定 PPARα 是控制这一关键功能的重要因素，并强调 PPARα 对于肠道营养介导的基因调控的重要性。
The selective absorption of nutrients and other food constituents in the small intestine is mediated by a group of transport proteins and metabolic enzymes, often collectively called 'intestinal barrier proteins'. An important receptor that mediates the effects of dietary lipids on gene expression is the peroxisome proliferator-activated receptor alpha (PPARα), which is abundantly expressed in enterocytes. In this study we examined the effects of acute nutritional activation of PPARα on expression of genes encoding intestinal barrier proteins. To this end we used triacylglycerols composed of identical fatty acids in combination with gene expression profiling in wild-type and PPARα-null mice. Treatment with the synthetic PPARα agonist WY14643 served as reference. We identified 74 barrier genes that were PPARα-dependently regulated 6 hours after activation with WY14643. For eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and oleic acid (OA) these numbers were 46, 41, and 19, respectively. The overlap between EPA-, DHA-, and WY14643-regulated genes was considerable, whereas OA treatment showed limited overlap. Functional implications inferred form our data suggested that nutrient-activated PPARα regulated transporters and phase I/II metabolic enzymes were involved in a) fatty acid oxidation, b) cholesterol, glucose, and amino acid transport and metabolism, c) intestinal motility, and d) oxidative stress defense. We identified intestinal barrier genes that were PPARα-dependently regulated after acute activation by fatty acids. This knowledge provides a better understanding of the impact dietary fat has on the barrier function of the gut, identifies PPARα as an important factor controlling this key function, and underscores the importance of PPARα for nutrient-mediated gene regulation in intestine.
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DOI：
10.1006/bbrc.1998.8842
发表时间：
1998-07-20
影响因子：
3.1
作者：
Fisher, MB;Zheng, YM;Rettie, AE
通讯作者：
Rettie, AE
影响因子：
64.8
作者：
Fu, J;Gaetani, S;Piomelli, D
通讯作者：
Piomelli, D
影响因子：
4.6
作者：
Bunger, Meike;van den Bosch, Heleen M.;Muller, Michael
通讯作者：
Muller, Michael
影响因子：
56.9
作者：
Altmann, SW;Davis, HR;Graziano, MP
通讯作者：
Graziano, MP
影响因子：
4.8
作者：
Haguenauer, A;Raimbault, S;Pecqueur, C
通讯作者：
Pecqueur, C