Plant-derived polyphenols regulate expression of miRNA paralogs miR-103/107 and miR-122 and prevent diet-induced fatty liver disease in hyperlipidemic mice
Plant-derived polyphenols regulate expression of miRNA paralogs miR-103/107 and miR-122 and prevent diet-induced fatty liver disease in hyperlipidemic mice
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DOI：
10.1016/j.bbagen.2012.03.020
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发表时间：
2012-07-01
影响因子：
3
通讯作者：
Beltran-Debon, Raul
中科院分区：
文献类型：
--
作者：
Joven, Jorge;Espinel, Eugenia;Beltran-Debon, Raul
背景：MicroRNA具有临床应用的潜力。植物来源的多酚的可能调节可能使用简单的饮食recommendations.Methods：我们评估了连续给予高剂量多酚调节市售高脂血症小鼠饮食诱导的脂肪肝疾病中肝脏代谢和microRNA表达的能力，使用完善和公认的程序，包括开发针对修饰槲皮素的新抗体。结果：体重增加，肝脂肪变性，肝组织组成的变化，胰岛素抵抗都减弱了连续管理的多酚。我们还证明了多酚的代谢物在免疫细胞和肝脂滴表面积累，这不仅表明生物利用度，而且可能直接作用于肝细胞。结论：多酚类化合物对脂肪肝有预防作用。mRNA和miRNA的差异表达也与脂质和葡萄糖代谢的变化以及5 '-腺苷一磷酸活化蛋白激酶的活化相关，这些效应不一定相关。miRNA通过不同的机制发挥作用，并且miRNA-mRNA相互作用难以用现有知识确定。此外，细胞模型通常会引起矛盾的结果与那些在动物models.General意义：我们的数据表明，植物来源的多酚应在人类中进行测试，作为预防，而不是治疗剂在调节肝脏脂肪酸的利用。可能存在多方面的作用机制，肝脏miRNA表达的调控在进一步研究中开辟了新的道路。(C)2012爱思唯尔有限公司版权所有。
Background: MicroRNAs have the potential for clinical application. Probable modulation by plant-derived polyphenols might open preventive measures using simple dietary recommendations.Methods: We assessed the ability of continuous administration of high-dose polyphenols to modulate hepatic metabolism and microRNA expression in diet-induced fatty liver disease in commercially available hyperlipidemic mice using well-established and accepted procedures that included the development of new antibodies against modified quercetin.Results: Weight gain, liver steatosis, changes in the composition of liver tissue, and insulin resistance were all attenuated by the continuous administration of polyphenols. We also demonstrated that metabolites of polyphenols accumulate in immune cells and at the surface of hepatic lipid droplets indicating not only bioavailability but a direct likely action on liver cells. The addition of polyphenols also resulted in changes in the expression of miR-103, miR-107 and miR-122.Conclusions: Polyphenols prevent fatty liver disease under these conditions. The differential expression of mRNAs and miRNAs was also associated with changes in lipid and glucose metabolism and with the activation of 5'-adenosine monophosphate-activated protein kinase, effects that are not necessarily connected. miRNAs function via different mechanisms and miRNA-mRNA interactions are difficult to ascertain with current knowledge. Further, cell models usually elicit contradictory results with those obtained in animal models.General significance: Our data indicate that plant-derived polyphenols should be tested in humans as preventive rather than therapeutic agents in the regulation of hepatic fatty acid utilization. A multi-faceted mechanism of action is likely and the regulation of liver miRNA expression blaze new trails in further research. (C) 2012 Elsevier B.V. All rights reserved.