Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710049, PR China.
Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710049, PR China.
Nutr Metab Cardiovasc Dis. 2020 Feb 10;30(2):320-329. doi: 10.1016/j.numecd.2019.09.025. Epub 2019 Oct 3.
This study aims to characterize the role of Irisin in obesity and early onset metabolic and vascular sequelae in Chinese children. Furthermore, we aim to examine whether Irisin mediate endothelial cells dysfunction and vascular inflammation which eventually leads to obesity.
We quantified plasma Irisin levels using enzyme-linked immunosorbent assay (ELISA) among 85 lean and 120 obese children, and assessed the association of Irisin levels with anthropometric, metabolic, cardiovascular and inflammatory parameters of obese children comparing with lean children. We further characterized the markers for endothelial cells and inflammation between obese and lean children to assess potential correlations. In addition, a potential direct effect of Irisin on the expression of endothelial adhesion molecules was assessed in human coronary artery endothelial cells. Irisin levels from obese children was significantly lower than lean children, and this reduced Irisin levels is correlated with certain physical parameters of studied children. Moreover, we identified significant inverse associations between inflammation markers of endothelial activation with Irisin levels in obese children. Multiple regression analyses confirm Irisin serves as a strong predictor of SDS-SBP, Ang-2, ICAM-1, E-selectin and hsCRP levels, independent of SDS-BMI. Lifestyle intervention results in a significant improvement of these cardiovascular and inflammatory parameters, and these were accompanied by a significant improvement of Irisin levels and weight loss. Finally, in the mediation effect model, our data showed that Irisin changes act as partial mediators of the relationship between SDS-BMI changes and changes in inflammatory and endothelial parameters for ICAM-1, E-selectin and hsCRP after controlling for covariates. Likewise, on the cellular level, Irisin inhibition hsCPR, ICAM-1 and E-selectin expression in endothelial cells, whereas Ang-2, VCAM-1 and eNOS expression were unaffected.
Our study showed that Irisin levels change may indicate the early stages of cardiovascular disease in obese children.
本研究旨在探讨鸢尾素在中国人肥胖及早期代谢和血管并发症中的作用。此外，我们还旨在研究鸢尾素是否介导内皮细胞功能障碍和血管炎症，从而导致肥胖。
我们使用酶联免疫吸附试验（ELISA）检测了 85 名正常体重儿童和 120 名肥胖儿童的血浆鸢尾素水平，并比较了肥胖儿童和正常体重儿童之间鸢尾素水平与人体测量学、代谢、心血管和炎症参数的相关性。我们进一步研究了肥胖儿童和正常体重儿童之间内皮细胞和炎症标志物的特征，以评估潜在的相关性。此外，我们还评估了鸢尾素对人冠状动脉内皮细胞表面黏附分子表达的潜在直接作用。肥胖儿童的鸢尾素水平明显低于正常体重儿童，且这种降低与所研究儿童的某些身体参数相关。此外，我们发现肥胖儿童的内皮激活炎症标志物与鸢尾素水平之间存在显著的负相关。多元回归分析证实，鸢尾素是 SDS-SBP、Ang-2、ICAM-1、E-选择素和 hsCRP 水平的强预测因子，独立于 SDS-BMI。生活方式干预可显著改善这些心血管和炎症参数，同时鸢尾素水平和体重也显著降低。最后，在中介效应模型中，我们的数据表明，在控制协变量后，鸢尾素的变化可以部分介导 SDS-BMI 变化与 ICAM-1、E-选择素和 hsCRP 等炎症和内皮参数变化之间的关系。同样，在细胞水平上，鸢尾素抑制 hsCPR、ICAM-1 和 E-选择素在内皮细胞中的表达，而 Ang-2、VCAM-1 和 eNOS 的表达不受影响。
本研究表明，鸢尾素水平的变化可能预示着肥胖儿童心血管疾病的早期阶段。
