Shu Linyi, Zhao Hang, Huang Wenli, Hou Guangsen, Song Guangyao, Ma Huijuan
Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, People's Republic of China.
Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, People's Republic of China.
Diabetes Metab Syndr Obes. 2020 Feb 14;13:391-403. doi: 10.2147/DMSO.S240956. eCollection 2020.
This study aimed to investigate how resveratrol (RSV) improves high-fat diet (HFD)-induced hepatic insulin resistance in mice via microRNA (miRNA) mmu-miR-363-3p in vitro and in vivo.
C57BL/6J mice were fed a HFD for 8 weeks to establish an insulin resistance model. The model mice were treated or not with RSV for 6 weeks. Differential miRNA expression in mouse liver tissues was analyzed by high-throughput sequencing. Mouse HepG2 cells were treated with palmitic acid (PA) to establish a cell model of insulin resistance. HepG2 cells were transfected with mmu-miR-363-3p inhibitor or mimic, and the expression of PI3K-Akt signaling pathway-related proteins was analyzed.
Based on the high-throughput sequencing analysis, mmu-miR-363-3p was identified as a major miRNA involved in the action of RSV on insulin resistance. Based on KEGG pathway enrichment analysis, PI3K-Akt signaling was found to be significantly enriched among differentially expressed miRNAs, and this pathway is closely related to insulin resistance. RSV treatment reduced the expression of FOXO1 and G6PC, which are downstream of the PI3K-Akt pathway. In the cell model, mmu-miR-363-3p inhibitor significantly suppressed p-Akt and p-PI3K levels, but enhanced those of FOXO1 and G6PC. In contrast, mmu-miR-363-3p mimic significantly enhanced the p-Akt and p-PI3K levels, but suppressed FOXO1 and G6PC expression, which was similar to the effect of RSV.
RSV improves insulin resistance by upregulating miRNA mmu-miR-363-3p via the PI3K-Akt pathway.
本研究旨在探讨白藜芦醇（RSV）如何通过微小RNA（miRNA）mmu-miR-363-3p在体外和体内改善高脂饮食（HFD）诱导的小鼠肝脏胰岛素抵抗。
将C57BL/6J小鼠喂食高脂饮食8周以建立胰岛素抵抗模型。对模型小鼠进行或不进行RSV处理6周。通过高通量测序分析小鼠肝脏组织中差异miRNA表达。用棕榈酸（PA）处理小鼠HepG2细胞以建立胰岛素抵抗细胞模型。用mmu-miR-363-3p抑制剂或模拟物转染HepG2细胞，并分析PI3K-Akt信号通路相关蛋白的表达。
基于高通量测序分析，mmu-miR-363-3p被鉴定为参与RSV对胰岛素抵抗作用的主要miRNA。基于KEGG通路富集分析，发现PI3K-Akt信号在差异表达的miRNA中显著富集，且该通路与胰岛素抵抗密切相关。RSV处理降低了PI3K-Akt通路下游的FOXO1和G6PC的表达。在细胞模型中，mmu-miR-363-3p抑制剂显著抑制p-Akt和p-PI3K水平，但增强了FOXO1和G6PC的水平。相反，mmu-miR-363-3p模拟物显著增强了p-Akt和p-PI3K水平，但抑制了FOXO1和G6PC表达，这与RSV的作用相似。
RSV通过PI3K-Akt通路上调miRNA mmu-miR-363-3p来改善胰岛素抵抗。
