Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits.

Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits.
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DOI:
10.3389/fphar.2020.619200
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发表时间:
2020
影响因子:
5.6
通讯作者:
Naccarati A
Naccarati A
中科院分区:
医学2区
文献类型:
--
作者:
Ferrero G;Carpi S;Polini B;Pardini B;Nieri P;Impeduglia A;Grioni S;Tarallo S;Naccarati A

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饮食对许多生理过程有很大的影响,而这些生理过程又对各种病理状况有重要影响。在这方面,microRNAs(miRNAs),一类小的非编码RNA在控制基因表达中发挥相关的表观遗传作用,可能代表饮食摄入和健康状态之间的介质。尽管在营养表观基因组学领域取得了巨大进展,但仍不清楚饮食如何调节miRNA表达,特别是特定营养素的摄入。我们通过对120名具有不同饮食习惯的健康志愿者(纯素食者,素食者和杂食者)的血浆样本进行小RNA测序来研究整个循环miRNome。根据先前在EPIC研究中验证的食物频率问卷中报告的信息,估计每个受试者的特定营养素饮食摄入量。因此,我们集中在23个天然化合物(NC)的类脂质,微量元素和维生素的摄入量。我们在13种NC的估计日摄入量和58种血浆miRNA的表达水平之间确定了78种显著相关性(rho > 0.300,p值< 0.05)。总体而言,维生素D,钠和维生素E与最大数量的miRNAs相关。所有确定的相关性在三个饮食组之间是一致的,其中22个通过年龄、性别和体重指数调整的广义线性回归模型分析被确认为显著的(p值< 0.05)。miR-23 a-3 p表达水平与不同的NC相关,包括与钠的显著正相关(rho = 0.377)和与脂质相关的NC和维生素E的显著负相关。相反,维生素D的估计摄入量与最高数量的循环miRNA的表达呈负相关,特别是miR-1277- 5 p(rho =-0.393)和miR-144- 3 p(rho =-0.393)。钠摄入相关miRNA的靶点的功能分析突出了与心脏发育相关的术语。对那些与维生素D摄入相关的miRNA靶点的类似方法显示,参与激素代谢的基因富集,而对慢性炎症的反应是涉及与维生素E摄入负相关的miRNA靶点的最高富集过程之一。我们的研究结果表明,通过习惯性饮食的营养影响循环miRNA谱,并强调这方面必须考虑在营养表观基因组学研究。
Diet has a strong influence on many physiological processes, which in turn have important implications on a variety of pathological conditions. In this respect, microRNAs (miRNAs), a class of small non-coding RNAs playing a relevant epigenetic role in controlling gene expression, may represent mediators between the dietary intake and the healthy status. Despite great advances in the field of nutri-epigenomics, it remains unclear how miRNA expression is modulated by the diet and, specifically, the intake of specific nutrients. We investigated the whole circulating miRNome by small RNA-sequencing performed on plasma samples of 120 healthy volunteers with different dietary habits (vegans, vegetarians, and omnivores). Dietary intakes of specific nutrients were estimated for each subject from the information reported in the food-frequency questionnaire previously validated in the EPIC study. We focused hereby on the intake of 23 natural compounds (NCs) of the classes of lipids, micro-elements, and vitamins. We identified 78 significant correlations (rho > 0.300, p-value < 0.05) among the estimated daily intake of 13 NCs and the expression levels of 58 plasma miRNAs. Overall, vitamin D, sodium, and vitamin E correlated with the largest number of miRNAs. All the identified correlations were consistent among the three dietary groups and 22 of them were confirmed as significant (p-value < 0.05) by age-, gender-, and body-mass index-adjusted Generalized Linear regression Model analysis. miR-23a-3p expression levels were related with different NCs including a significant positive correlation with sodium (rho = 0.377) and significant negative correlations with lipid-related NCs and vitamin E. Conversely, the estimated intake of vitamin D was negatively correlated with the expression of the highest number of circulating miRNAs, particularly miR-1277-5p (rho = −0.393) and miR-144-3p (rho = −0.393). Functional analysis of the targets of sodium intake-correlated miRNAs highlighted terms related to cardiac development. A similar approach on targets of those miRNAs correlated with vitamin D intake showed an enrichment in genes involved in hormone metabolisms, while the response to chronic inflammation was among the top enriched processes involving targets of miRNAs negatively related with vitamin E intake. Our findings show that nutrients through the habitual diet influence circulating miRNA profiles and highlight that this aspect must be considered in the nutri-epigenomic research.
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