Insulin resistance (IR) is a state when the physiological amount of insulin is not sufficient to evoke proper action, that is, glucose uptake. Numerous conditions lead to IR, including epigenetic components. Epigenetic modifications, associated with obesity and IR are one of the main mechanisms leading to IR pathogenesis.

The adipose tissue samples (subcutaneous (SAT) and visceral (VAT)) were collected during abdominal surgery from 40 patients of a wide range of BMI, age, and insulin resistance ratios (F = 9, M = 31). IR was induced in 3T3-L1 adipocytes and human adipocytes collected from SAT and VAT of healthy subjects. Global and site-specific histone modifications (H3K4me3 and H3K9/14ac) were determined.

We found lower histone modifications in adipose tissue of IR patients. Furthermore, numerous genes regulating insulin action (PPARG, SLC2A4, ADIPOQ) were differently marked by histone methylation and acetylation. Moreover, we noticed that epigenetic changes appear as soon as 72 h following IR induction. The epigenetic changes appeared to be mediated through the SIRT family.

Based on obtained results, the histone marks related to insulin resistance mostly concerned PPARG and SLC2A4 genes. Furthermore, our results proved a vital role of the SIRT family in insulin action and IR pathogenesis.

胰岛素抵抗 (IR) 是当胰岛素的生理量不足以引起适当的作用，即葡萄糖摄取时的状态。许多条件导致 IR，包括表观遗传成分。与肥胖和 IR 相关的表观遗传修饰是导致 IR 发病的主要机制之一。

脂肪组织样本（皮下 (SAT) 和内脏 (VAT)）是在腹部手术期间从 40 名不同 BMI、年龄和胰岛素抵抗比率（F = 9，M = 31）的患者中收集的。在从健康受试者的 SAT 和 VAT 收集的 3T3-L1 脂肪细胞和人类脂肪细胞中诱导 IR。确定了全局和特定于站点的组蛋白修饰（H3K4me3 和 H3K9/14ac）。

我们发现 IR 患者脂肪组织中的组蛋白修饰较低。此外，许多调节胰岛素作用的基因（PPARG、SLC2A4、ADIPOQ）以不同的组蛋白甲基化和乙酰化标记。此外，我们注意到表观遗传变化在 IR 诱导后 72 小时即出现。表观遗传变化似乎是通过SIRT家族介导的。

根据获得的结果，与胰岛素抵抗相关的组蛋白标记主要涉及PPARG和SLC2A4基因。此外，我们的结果证明了 SIRT 家族在胰岛素作用和 IR 发病机制中的重要作用。