Department of Forensic Medicine, Department of Molecular Techniques, Wrocław Medical University, Skłodowskiej-Curie 52, 50-369 Wroclaw, Poland.
Department of General, Minimally Invasive and Endocrine Surgery, Wrocław Medical University, Borowska 213, 50-556 Wroclaw, Poland.
Genes (Basel). 2022 Feb 2;13(2):294. doi: 10.3390/genes13020294.
A higher level of expression in obesity and insulin resistance was observed in both human and mouse WAT. In our research, we analyzed the influence of insulin resistance on epigenetic modification within the promoter region gene and the potential influence of these modifications on its expression. Studies were performed using two cell models for the analysis: human, preadipocytes derived from adipose (visceral and subcutaneous) tissues and murine 3T3-L1 fibroblasts. We demonstrated a significant increase in the expression level, promoter region methylation, and histone 3 epigenetic modifications: H3K4me and H3K9/14ac, in insulin resistance cells (IR) from SAT cell culture. In IR cells from VAT cell culture, we observed decreased expression with a simultaneous increase of promoter region methylation. In IR cells from 3T3L1 cell culture, we observed the increased expression of as well as the decreased levels of methylation in the promoter region and histone methylation (H3K4me) and acetylation (H3K9/14ac). The presented analyses suggest a potential impact of epigenetic modifications on gene expression and a potential mutual influence of epigenetic modifications on each other or the activation of specific epigenetic regulation at a different stage of the development of insulin resistance in cells.
在肥胖和胰岛素抵抗的人类和小鼠 WAT 中均观察到更高水平的表达。在我们的研究中,我们分析了胰岛素抵抗对基因启动子区域内表观遗传修饰的影响,以及这些修饰对其表达的潜在影响。使用两种细胞模型进行了研究:源自脂肪(内脏和皮下)组织的人前脂肪细胞和鼠 3T3-L1 成纤维细胞。我们证明了胰岛素抵抗细胞(IR)中基因表达水平、启动子区域甲基化和组蛋白 3 表观遗传修饰(H3K4me 和 H3K9/14ac)显著增加。在来自 VAT 细胞培养的 IR 细胞中,我们观察到表达减少,同时启动子区域甲基化增加。在来自 3T3L1 细胞培养的 IR 细胞中,我们观察到表达增加,同时启动子区域甲基化减少和组蛋白甲基化(H3K4me)和乙酰化(H3K9/14ac)减少。提出的分析表明,表观遗传修饰可能对基因表达有潜在影响,并且表观遗传修饰之间可能相互影响,或者在细胞胰岛素抵抗发展的不同阶段激活特定的表观遗传调节。