Postprandial Circulating miRNAs in Response to a Dietary Fat Challenge
Postprandial Circulating miRNAs in Response to a Dietary Fat Challenge
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DOI：
10.3390/nu11061326
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发表时间：
2019-06-01
期刊：
影响因子：
5.9
通讯作者：
Davalos, Alberto
中科院分区：
文献类型：
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作者：
Mantilla-Escalante, Diana C.;Lopez de las Hazas, Maria-Carmen;Davalos, Alberto
餐后脂血症具有许多生理病理学影响，其中一些会增加心血管疾病的风险。 MicroRNA (miRNA) 几乎存在于所有生物体液中，但其餐后动力学却很少被描述。我们的目的是分析响应脂肪挑战的循环 miRNA。脂质饲喂后两小时，通过实时 PCR 评估了小鼠血浆中总共 641 个循环 miRNA。筛选肠道特异性 Dicer 缺失的小鼠，以鉴定肠道释放的潜在 miRNA。总共选择了 68 个 miRNA 进行进一步验证。最终验证了 10 种循环 miRNA 对餐后脂血症有反应，包括 miR-206-3p、miR-543-3p、miR-466c-5p、miR-27b-5p、miR-409-3p、miR-340-3p、miR-1941-3p、miR-10a-3p、miR-125a-3p 和miR-468-3p。对它们可能的来源/目标组织的分析表明，选定的 miRNA 在肝脏、肠道、大脑或骨骼肌中富集。 miR-206、miR-27b-5p 和 miR-409-3p 在健康人类中得到验证。对他们预测的靶基因的分析表明，它们可能参与小鼠的胰岛素/胰岛素样生长因子 (insulin/IGF)、血管生成、胆囊收缩素 B 受体信号通路 (CCKR)、炎症或 Wnt 通路，以及人类的血小板衍生生长因子 (PDGF) 和 CCKR 信号通路。因此，目前的研究表明，某些 miRNA 会响应脂肪膳食而释放到循环中，这表明它们是脂质代谢的潜在新治疗靶点。
Postprandial lipemia has many physiopathological effects, some of which increase the risk of cardiovascular disease. MicroRNAs (miRNAs) can be found in almost all biological fluids, but their postprandial kinetics are poorly described. We aimed to profile circulating miRNAs in response to a fat challenge. In total, 641 circulating miRNAs were assessed by real-time PCR in plasmas from mice two hours after lipid gavage. Mice with intestine-specific loss of Dicer were screened to identify potential miRNAs released by the intestine. A total of 68 miRNAs were selected for further validation. Ten circulating miRNAs were finally validated as responsive to postprandial lipemia, including miR-206-3p, miR-543-3p, miR-466c-5p, miR-27b-5p, miR-409-3p, miR-340-3p, miR-1941-3p, miR-10a-3p, miR-125a-3p, and miR-468-3p. Analysis of their possible tissues of origin/target showed an enrichment of selected miRNAs in liver, intestine, brain, or skeletal muscle. miR-206, miR-27b-5p, and miR-409-3p were validated in healthy humans. Analysis of their predicted target genes revealed their potential involvement in insulin/insulin like growth factor (insulin/IGF), angiogenesis, cholecystokinin B receptor signaling pathway (CCKR), inflammation or Wnt pathways for mice, and in platelet derived growth factor (PDGF) and CCKR signaling pathways for humans. Therefore, the current study shows that certain miRNAs are released in the circulation in response to fatty meals, proposing them as potential novel therapeutic targets of lipid metabolism.