胰岛素抵抗和 2 型糖尿病等代谢紊乱与脑功能障碍和认知缺陷有关，尽管其基本分子机制仍然难以捉摸。据报道，表观遗传因素（例如非编码 RNA）可介导营养相关信号的分子效应。在这里，我们研究了高脂饮食（HFD）诱导的代谢疾病的成熟实验模型的海马体中 miRNA 表达谱的变化。与标准饮食喂养的对照组相比，我们观察到 HFD 小鼠海马体中 69 种 miRNA 的表达增加，63 种 miRNA 的表达减少。通过生物信息学分析，我们确定了失调 miRNA 的许多潜在靶标，精确定位了多个差异调节 miRNA 靶向的调节神经可塑性的基因子集。我们还验证了这些突触和非突触蛋白的表达，证实了突触结合蛋白 1 (SYT1)、钙/钙调蛋白依赖性蛋白激酶 I δ (CaMK1D)、N-甲基-D-天冬氨酸谷氨酸受体 2B 亚基 (GRIN2B) 的下调HFD 海马中的 DNA 结合蛋白特殊 AT 丰富序列结合蛋白 2 (SATB2) 和 RNA 结合蛋白细胞质多腺苷酸化元件结合蛋白 1 (CPEB1) 和神经肿瘤腹侧抗原 1 (NOVA1)老鼠。总之，我们的研究提供了与 HFD 相关的 miRNA 景观的快照，这些 miRNA 可能参与与代谢紊乱相关的大脑功能的改变。通过阐明特定的 miRNA-mRNA 相互作用，我们的研究有助于更深入地了解 HFD 对突触功能影响的分子机制。© 2024。作者。

Metabolic disorders such as insulin resistance and type 2 diabetes are associated with brain dysfunction and cognitive deficits, although the underpinning molecular mechanisms remain elusive. Epigenetic factors, such as non-coding RNAs, have been reported to mediate the molecular effects of nutrient-related signals. Here, we investigated the changes of miRNA expression profile in the hippocampus of a well-established experimental model of metabolic disease induced by high fat diet (HFD). In comparison to the control group fed with standard diet, we observed 69 miRNAs exhibiting increased expression and 63 showing decreased expression in the HFD mice's hippocampus. Through bioinformatics analysis, we identified numerous potential targets of the dysregulated miRNAs, pinpointing a subset of genes regulating neuroplasticity that were targeted by multiple differentially modulated miRNAs. We also validated the expression of these synaptic and non-synaptic proteins, confirming the downregulation of Synaptotagmin 1 (SYT1), calcium/calmodulin dependent protein kinase I delta (CaMK1D), 2B subunit of N-methyl-D-aspartate glutamate receptor (GRIN2B), the DNA-binding protein Special AT-Rich Sequence-Binding Protein 2 (SATB2), and RNA-binding proteins Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) and Neuro-oncological ventral antigen 1 (NOVA1) in the hippocampus of HFD mice. In summary, our study offers a snapshot of the HFD-related miRNA landscape potentially involved in the alterations of brain functions associated with metabolic disorders. By shedding light on the specific miRNA-mRNA interactions, our research contributes to a deeper understanding of the molecular mechanisms underlying the effects of HFD on the synaptic function.© 2024. The Author(s).