Epigenetic modifications of nuclear and mitochondrial DNA are associated with the disturbance of serum iron biomarkers among the metabolically unhealthy obesity school-age children.

Abstract

Background: Serum iron biomarkers are disordered on the progression of obesity and its associated metabolic syndrome (MetS). However, limited evidence is explored the interactions between serum iron biomarkers and the incidence of MetS. Thus, the purpose of this study is to discuss whether epigenetic modifications of nuclear and mitochondrial DNA (mtDNA) are associated with the disturbance of serum iron biomarkers among the metabolically unhealthy obesity (MUO) school-age children.

Methods: A representative cross-sectional study was performed using the data from 104 obesity school-age children, while the subjects without obesity were as controls (n = 65). Then, the 104 obesity subjects were defined as metabolically healthy obesity (MHO, n = 60) and MUO (n = 44) subgroups according to whether they were accompanied with MetS. Their serum metabolic indicators, transferrin receptor 1 (TFR1), transferrin (TF) and genome-wide methylation were determined by the Elisa method. Moreover, the methylation levels of TFR1 and TF were measured by the Bisulfite sequencing PCR (BSP-PCR). Furthermore, the copy number (mtDNA-CN) and methylation of mtDNA were detected by the RT-PCR, while the semi-long RT-PCR was then used to estimate the lesions of mtDNA.

Results: Compared with the control and MHO groups, the levels of MetS related indicators, anthropological characteristics and 8-OHdG were higher, and the concentrations of CAT, GSH-Px, TF, TFR1 and genome-wide methylation were lower in the MUO group in a BMI-independent manner (P < 0.05). Then, the contents of serum iron were lower in both the MHO and MUO groups than those in the control group (P < 0.017). Moreover, they were positively related with the contents of serum CAT and GSH-Px, and negatively with 8-OHdG, TF and TFR1 (P < 0.05). Furthermore, the methylation patterns on the TF, TFR1 and mtDNA were higher in the MUO group than those in the MHO and control groups (P < 0.017), which were negatively correlated with their serum contents (P < 0.05). Meanwhile, the ratio of methylated/unmethylated mtDNA was significantly associated with their mtDNA-CN and lesions (P < 0.05).

Conclusions: Our findings suggested that the impairments on the epigenetic modifications of nuclear (genome-wide DNA, TF and TFR1) and mtDNA were associated with the disturbance of serum iron biomarkers to involve in the pathophysiology of MetS among the school-age MUO children.

Trial registration: This study was approved by the Ethics Committee of Beijing Children's Hospital affiliated to Capital Medical University (No. IEC-C-006-A04-V.06), which was also registered at the website of http://www.chictr.org.cn/showproj.aspx?proj=4673 (No: ChiCTR-OCH-14004900).