Department of Forensic Medicine, Molecular Techniques Unit, Wroclaw Medical University, Curie-Sklodowskiej 52, 50-369, Wroclaw, Poland.
Department and Division of Surgical Didactics, Wroclaw Medical University, M. Curie-Sklodowskiej 66, 50-369, Wroclaw, Poland.
Int J Obes (Lond). 2021 Mar;45(3):650-658. doi: 10.1038/s41366-020-00729-7. Epub 2021 Jan 7.
Both obesity and insulin resistance are characterized by severe long-term changes in the expression of many genes of importance in the regulation of metabolism. Because these changes occur throughout life, as a result of external factors, the disorders of gene expression could be epigenetically regulated.
MATERIALS/METHODS: We analyzed the relationship between obesity and insulin resistance in enrolled patients by means of evaluation of the expression rate of numerous genes involved in the regulation of adipocyte metabolism and energy homeostasis in subcutaneous and visceral adipose tissue depots. We also investigated global and site-specific DNA methylation as one of the main regulators of gene expression. Visceral and subcutaneous adipose tissue biopsies were collected from 45 patients during abdominal surgery in an age range of 40-60 years.
We demonstrated hypermethylation of PPARG, INSR, SLC2A4, and ADIPOQ promoters in obese patients with insulin resistance. Moreover, the methylation rate showed a negative correlation with the expression of the investigated genes. More, we showed a correlation between the expression of PPARG and the expression of numerous genes important for proper insulin action. Given the impact of PPARγ on the regulation of the cell insulin sensitivity through modulation of insulin pathway genes expression, hypermethylation in the PPARG promoter region may constitute one of the epigenetic pathways in the development of insulin resistance in obesity.
Our research shows that epigenetic regulation through excessive methylation may constitute a link between obesity and subsequent insulin resistance.
肥胖和胰岛素抵抗的特征是许多对代谢调节具有重要意义的基因表达发生严重的长期变化。由于这些变化是由于外部因素而在整个生命过程中发生的，因此基因表达的紊乱可能受到表观遗传调控。
材料/方法：我们通过评估参与调节脂肪细胞代谢和能量稳态的许多基因在外周和内脏脂肪组织中的表达率，分析了纳入患者中肥胖和胰岛素抵抗之间的关系。我们还研究了作为基因表达主要调控因子之一的整体和特定部位的 DNA 甲基化。在年龄为 40-60 岁的腹部手术期间，从 45 名患者中采集了内脏和皮下脂肪组织活检。
我们证明了胰岛素抵抗肥胖患者的 PPARG、INSR、SLC2A4 和 ADIPOQ 启动子发生了过度甲基化。此外，甲基化率与研究基因的表达呈负相关。此外，我们还显示了 PPARG 表达与许多对胰岛素功能正常至关重要的基因表达之间存在相关性。鉴于 PPARγ 对细胞胰岛素敏感性的调节作用是通过调节胰岛素途径基因的表达来实现的，因此 PPARG 启动子区域的过度甲基化可能是肥胖导致胰岛素抵抗的表观遗传途径之一。
我们的研究表明，通过过度甲基化进行的表观遗传调控可能是肥胖与随后的胰岛素抵抗之间的联系。
