Insulin-like growth factor binding-protein 2 (IGFBP-2) is secreted by differentiating white adipocytes. Clinical studies demonstrate that circulating IGFBP-2 levels associated inversely with body mass index (BMI) and insulin resistance. To explore possible epigenetic changes of the IGFBP2 gene in obesity, we analyzed DNA methylation and mRNA expression in adipocytes from different depots. Healthy lean controls (BMI = 24.5 ± 0.3 kg/m², n = 19) and obese subjects (BMI > 35 kg/m², n = 24) were recruited. All subjects were Swedish Caucasian. Visceral abdominal adipose tissue (VAT) and subcutaneous adipose tissue (SAT) fragments were homogenized. Genomic DNA and total RNAs were extracted. Four CpG sites in the IGFBP2 gene promoter region were analyzed with bisulfite pyrosequencing. IGFBP2 gene expression at mRNA levels was determined with TaqMan real time RT-PCR. Serum samples were used for measurement of circulating IGFBP-2 and leptin levels. IGFBP2 DNA methylation levels in VAT were increased in obese subjects compared with controls (P < .05). By contrast, IGFBP2 mRNA expression levels in VAT were lower in obesity subjects than in controls (P < .05). In SAT, IGFBP2 DNA methylation and RNA expression levels were lower than in VAT, irrespective of obesity. Obese subjects demonstrated increased serum leptin levels (P < .001) and reduced serum IGFBP-2 levels compared to controls (P < .05). In conclusion, the current study demonstrates that IGFBP2 DNA methylation levels are increased in VAT from obese subjects. This suggests that IGFBP-2 is epigenetically regulated in abdominal obesity.

胰岛素样生长因子结合蛋白2（IGFBP-2）通过分化白色脂肪细胞而分泌。临床研究表明，循环中的IGFBP-2水平与体重指数（BMI）和胰岛素抵抗呈负相关。为了探索肥胖中IGFBP2基因可能的表观遗传变化，我们分析了来自不同贮库的脂肪细胞中的DNA甲基化和mRNA表达。 招募健康的瘦身对照（BMI = 24.5±0.3 kg / m ²，n  = 19）和肥胖受试者（BMI> 35 kg / m ²，n = 24）。所有受试者均为瑞典白人。将内脏腹部脂肪组织（VAT）和皮下脂肪组织（SAT）片段均质化。提取基因组DNA和总RNA。四个CpG网站用亚硫酸氢盐焦磷酸测序法分析IGFBP2基因启动子区域。用TaqMan实时RT-PCR测定mRNA水平的IGFBP2基因表达。血清样品用于测量循环IGFBP-2和瘦素水平。与对照组相比，肥胖受试者的VAT中IGFBP2 DNA甲基化水平增加（P  <.05）。相比之下，肥胖受试者的VAT中IGFBP2 mRNA表达水平低于对照组（P  <.05）。在SAT中，无论肥胖与否，IGFBP2 DNA甲基化和RNA表达水平均低于VAT。肥胖受试者表现出血清瘦素水平升高（P <0.001），并且血清IGFBP-2水平低于对照组（P  <.05）。总之，当前的研究表明，肥胖受试者的VAT中IGFBP2 DNA甲基化水平增加。这表明IGFBP-2在腹部肥胖中受表观遗传调控。