miRNA-10a is rhythmically expressed and regulates genes involved in lipid and glucose metabolism. However, the effects of miRNA-10a on obesity and glucose intolerance, as well as on the diurnal pattern of expression of circadian clock genes, remain unknown. We explored the effects of miRNA-10a-5p on insulin resistance and on the diurnal patterns of serum triglycerides and gut microbiota in high-fat diet- (HFD-) fed mice. The results showed that oral administration of miRNA-10a-5p significantly prevented body weight gain and improved glucose tolerance and insulin sensitivity in HFD-fed mice. Administration of miRNA-10a-5p also maintained the diurnal rhythm of Clock, Per2, and Cry1 expression, as well as serum glucose and triglyceride levels. Surprisingly, the diurnal oscillations of three genera of microbes, Oscillospira, Ruminococcus, and Lachnospiraceae, disrupted by HFD feeding, maintained by administration of miRNA-10a-5p. Moreover, a strong positive correlation was found between hepatic Clock expression and relative abundance of Lachnospiraceae, both in control mice () and in mice administered miRNA-10a-5p (). Furthermore, we found that along with changes in Lachnospiraceae abundance, butyrate content in the feces maintained a diurnal rhythm after miRNA-10a-5p administration in HFD-fed mice. In conclusion, we suggest that miRNA-10a-5p may improve HFD-induced glucose intolerance and insulin resistance through the modulation of the diurnal rhythm of Lachnospiraceae and its metabolite butyrate. Therefore, miRNA-10a-5p may have preventative properties in subjects with metabolic disorders.

中文翻译：

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miRNA-10a-5p 减轻胰岛素抵抗并维持高脂饮食喂养小鼠的甘油三酯和肠道微生物群的昼夜模式。

miRNA-10a 有节奏地表达并调节参与脂质和葡萄糖代谢的基因。然而，miRNA-10a 对肥胖和葡萄糖耐受不良以及昼夜节律时钟基因表达模式的影响仍然未知。我们探讨了 miRNA-10a-5p 对胰岛素抵抗以及高脂饮食 (HFD) 喂养小鼠血清甘油三酯和肠道微生物群的昼夜模式的影响。结果表明，口服 miRNA-10a-5p 可显着防止 HFD 喂养小鼠的体重增加并改善葡萄糖耐量和胰岛素敏感性。miRNA-10a-5p 的给药也维持了Clock、Per2和Cry1的昼夜节律表达，以及血清葡萄糖和甘油三酯水平。令人惊讶地，三个属微生物的日振荡，Oscillospira，瘤胃球菌属，以及毛螺，通过HFD馈送破坏，保持通过的miRNA-10A-5P的给药。此外，在对照小鼠中，肝脏时钟表达与毛螺菌科的相对丰度之间存在很强的正相关关系。)和在施用 miRNA-10a-5p 的小鼠中 (）。此外，我们发现，随着毛螺菌科丰度的变化，在喂食 HFD 的小鼠中施用 miRNA-10a-5p 后，粪便中的丁酸盐含量保持了昼夜节律。总之，我们认为 miRNA-10a-5p 可能通过调节毛螺科及其代谢物丁酸盐的昼夜节律来改善 HFD 诱导的葡萄糖耐受不良和胰岛素抵抗。因此，miRNA-10a-5p 可能对患有代谢紊乱的受试者具有预防作用。