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载脂蛋白 E 决定了膳食马尿酸在小鼠肝脏中的转录谱。

Apolipoprotein E determines the hepatic transcriptional profile of dietary maslinic acid in mice.

机构信息

Departamento de Bioquímica y Biología Molecular y Celular, Instituto Aragonés de Ciencias de la Salud (Universidad de Zaragoza-Dirección Salud del Gobierno de Aragón), E-50013 Zaragoza, Spain.

出版信息

J Nutr Biochem. 2009 Nov;20(11):882-93. doi: 10.1016/j.jnutbio.2008.08.003. Epub 2008 Nov 6.

DOI:10.1016/j.jnutbio.2008.08.003
PMID:18993045
Abstract

The hypothesis that the maslinic acid (MA) of olive oil (OO) dramatically influences hepatic gene expression was tested in mice. Two OOs only differing in the presence of MA were prepared. Using DNA microarrays, we analyzed hepatic gene expression in apolipoprotein E (apoE)-deficient mice with a C57BL/6J genetic background that were fed with isocaloric, isonitrogenous diets containing either 10% (w/w) OO or 10% MA-enriched OO. As an initial screening of potential candidate genes involved in a differential response, this study further considered only genes with remarkably modified expression (signal log(2) ratio higher than1.5 or lower than -1.5). The nine genes fulfilling these prerequisites were confirmed by quantitative reverse transcriptase polymerase chain reaction and analyzed in C57BL/6J wild-type mice. Only Cyp2b9, Cyp2b13 and Dbp expressions appeared significantly increased, and Marco was significantly decreased in apoE-deficient mice receiving the MA-enriched diet. Dbp was up-regulated to an extent depending on the genetic background of the mice and negatively associated with the expression of Marco, a gene strongly up-regulated by the absence of apoE. These expression changes could be used as markers of the intake of the MA-enriched OO and are influenced by genetic background generated by the absence or the presence of apoE. Overall, these results (a) indicate that MA in virgin OO is highly active in controlling hepatic gene expression and (b) highlight the important interaction between the response to MA and the presence of apoE. They also confirm that virgin OO cannot be simplistically classified as monounsaturated fatty-enriched oil without paying attention to its active minor components.

摘要

研究假设橄榄油中的马尿酸(MA)可显著影响肝脏基因表达,并在载脂蛋白 E(apoE)缺陷小鼠中进行了验证。该研究制备了仅存在 MA 差异的两种橄榄油。使用 DNA 微阵列,我们分析了具有 C57BL/6J 遗传背景的 apoE 缺陷小鼠的肝脏基因表达,这些小鼠喂食等热量、等氮饮食,其中包含 10%(w/w)的橄榄油或富含 MA 的橄榄油。作为对差异反应相关潜在候选基因的初步筛选,本研究仅考虑了表达明显改变的基因(信号对数比高于 1.5 或低于-1.5)。通过定量逆转录聚合酶链反应进一步证实了满足这些前提条件的 9 个基因,并在 C57BL/6J 野生型小鼠中进行了分析。仅 Cyp2b9、Cyp2b13 和 Dbp 的表达明显增加,而 apoE 缺陷小鼠接受富含 MA 的饮食时 Marco 的表达明显降低。Dbp 的上调程度取决于小鼠的遗传背景,与 apoE 缺失强烈上调的 Marco 基因的表达呈负相关。这些表达变化可作为摄入富含 MA 的橄榄油的标志物,并且受到由 apoE 缺失或存在引起的遗传背景的影响。总的来说,这些结果表明:(a)橄榄油中的 MA 可高度活跃地控制肝脏基因表达;(b)强调了对 MA 的反应与 apoE 存在之间的重要相互作用;(c)还证实了如果不注意其活性的次要成分,不能简单地将 virgin OO 归类为富含单不饱和脂肪酸的油。

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