Reduced circulating mitochondrial DNA integrity and increased DNA oxidation in preclinical and clinical pediatric...

Childhood obesity is associated with cardiometabolic dysfunction. Oxidative stress and mitochondrial damage may contribute to this process, but their role children with excess adiposity and preserved metabolic parameters remains unclear. Circulating mitochondrial DNA (c-mtDNA) has emerged as a potential biomarker of mitochondrial injury and systemic stress. This study evaluated oxidative DNA damage and c-mtDNA integrity (c-mtDNAi) in children at different obesity phenotypes as indicators of metabolic risk.

A total of 103 children aged 6-12 years were classified as normal-weight controls, preclinical obesity (pOb), or clinical obesity (cOb) using the 2025-OCF criteria based on biochemical alterations. Oxidative circulating DNA damage was quantified using 8-hydroxy-2'-deoxyguanosine (8-OH-dG). The c-mtDNAi was evaluated by long-range PCR. Lipid metabolism markers were measured, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), the triglyceride-to-HDL cholesterol (TG/HDL-C) ratio, and the triglyceride-glucose (TyG) index. Plasma cytokine levels were quantified using flow cytometry.

Both preclinical Ob and clinical Ob groups showed significantly higher 8-OH-dG levels and reduced c-mtDNAi compared with controls (p < 0.0001), indicating mtDNA damage. 8-OH-dG was positively correlated with TG levels, the TG/HDL-C ratio, and the TyG index, whereas c-mtDNAi exhibited inverse correlations with these lipid-related markers and correlated positively with HDL-C levels. In multivariable analyses, waist circumference percentile remained independently associated with both 8-OH-dG and c-mtDNAi after adjustment for TG and HDL-C. Cytokine concentrations were elevated in pOb and cOb groups compared with controls.

Oxidative DNA damage and reduced c-mtDNAi were detected in both pOb and cOb compared with controls, indicating mitochondrial and oxidative alterations associated with excess adiposity. These findings indicate that c-mtDNA integrity and 8-OH-dG may represent biomarkers associated with excess adiposity and metabolic risk in pediatric obesity.

ClinicalTrials.gov, TRN: NCT02320110, Registration date: 02 December 2014.