Associations between hepatic miRNA expression, liver triacylglycerols and gut microbiota during metabolic adaptation to high-fat diet in mice.
Associations between hepatic miRNA expression, liver triacylglycerols and gut microbiota during metabolic adaptation to high-fat diet in mice.
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DOI：
10.1007/s00125-017-4209-3
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发表时间：
2017-04
期刊：
影响因子：
8.2
通讯作者：
Serino M
中科院分区：
文献类型：
--
作者：
Blasco-Baque V;Coupé B;Fabre A;Handgraaf S;Gourdy P;Arnal JF;Courtney M;Schuster-Klein C;Guardiola B;Tercé F;Burcelin R;Serino M
尽管目前代谢性疾病大流行，但我们对食用高脂饮食(HFD)的人代谢改变发展的多样性本质的理解仍然很差。我们最近在喂食HFD的小鼠身上证明了一种心脏代谢适应，其特征是特定的肠道和牙周微生物区系。由于肝脏疾病的严重程度是由特定的microRNA(MiRNA)特征表征的，而肠道微生物区系是肝病和miRNA表达的关键驱动因素，因此我们分析了三种肝脏miRNA的表达，并研究了它们与肝脏三酰甘油含量和肠道微生物区系的相关性。两组4周龄C57BL/6野生型(WT)雄性小鼠(n = 62和n = 96)饲喂高脂饲料3个月，建立代谢适应模型。另外，8周龄的C57BL/6小鼠，无论是WT小鼠还是不同基因型的C57BL/6小鼠，具有不同的肠道微生物群(ob/ob，Nod1，CD14基因敲除[CD14KO]和NOD2)或没有肠道微生物群(无菌小鼠)，分别喂以正常饮食。测定血糖指数、体重、血糖和肝脏三酰甘油水平。对肠道(盲肠)微生物区系进行了焦糖测序分析。为了分析肝脏miRNA的表达，对提取的总miRNA样本进行实时荧光定量聚合酶链式反应。数据分析采用双因素方差分析，然后进行Dunnett后检验，或未配对的学生t检验。还进行了聚类分析和多变量分析。我们的结果表明，miR-181a、miR-666和miR-21在原代小鼠肝细胞中的表达受脂多糖的剂量依赖性调控。肠道微生物区系中，菲米库斯与肝脏三酰甘油水平呈正相关，变形杆菌和类酸杆菌与肝脏三酰甘油水平呈负相关。此外，鱼体相对丰度与肝脏miR-666和miR-21的表达呈负相关。相反，酸性芽孢杆菌的相对丰度与miR-21呈正相关。我们认为，肝脏miRNA、肝脏三酰甘油和肠道微生物区系作为一种新的三联体参与了肠道微生物区系在HFD代谢适应过程中调控肝脏病理生理的分子机制。这篇文章的在线版本(doi：10.1007/s00125.0174209-3)包含经同行审查但未经编辑的补充材料，授权用户可以使用。
Despite the current pandemic of metabolic diseases, our understanding of the diverse nature of the development of metabolic alterations in people who eat a high-fat diet (HFD) is still poor. We recently demonstrated a cardio-metabolic adaptation in mice fed an HFD, which was characterised by a specific gut and periodontal microbiota profile. Since the severity of hepatic disease is characterised by specific microRNA (miRNA) signatures and the gut microbiota is a key driver of both hepatic disease and miRNA expression, we analysed the expression of three hepatic miRNA and studied their correlation with hepatic triacylglycerol content and gut microbiota. Two cohorts of C57BL/6 4-week-old wild-type (WT) male mice (n = 62 and n = 96) were fed an HFD for 3 months to provide a model of metabolic adaptation. Additionally 8-week-old C57BL/6 mice, either WT or of different genotypes, with diverse gut microbiota (ob/ob, Nod1, Cd14 knockout [Cd14KO] and Nod2) or without gut microbiota (axenic mice) were fed a normal chow diet. Following which, glycaemic index, body weight, blood glucose levels and hepatic triacylglycerol levels were measured. Gut (caecum) microbiota taxa were analysed by pyrosequencing. To analyse hepatic miRNA expression, real-time PCR was performed on total extracted miRNA samples. Data were analysed using two-way ANOVA followed by the Dunnett’s post hoc test, or by the unpaired Student’s t test. A cluster analysis and multivariate analyses were also performed. Our results demonstrated that the expression of miR-181a, miR-666 and miR-21 in primary murine hepatocytes is controlled by lipopolysaccharide in a dose-dependent manner. Of the gut microbiota, Firmicutes were positively correlated and Proteobacteria and Bacteroides acidifaciens were negatively correlated with liver triacylglycerol levels. Furthermore, the relative abundance of Firmicutes was negatively correlated with hepatic expression of miR-666 and miR-21. In contrast, the relative abundance of B. acidifaciens was positively correlated with miR-21. We propose the involvement of hepatic miRNA, liver triacylglycerols and gut microbiota as a new triad that underlies the molecular mechanisms by which gut microbiota governs hepatic pathophysiology during metabolic adaptation to HFD. The online version of this article (doi:10.1007/s00125-017-4209-3) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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作者：
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通讯作者：
Burcelin R
影响因子：
4.5
作者：
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