The Children's Obesity Clinic, European Centre of Management (EASO), Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
The Children's Obesity Clinic, European Centre of Management (EASO), Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Free Radic Biol Med. 2020 Aug 1;155:81-86. doi: 10.1016/j.freeradbiomed.2020.05.009. Epub 2020 May 25.
Oxidative stress may play an important role in childhood obesity and increased cardiometabolic risk. 8-oxo-7,8-dihydroguanosine (8-oxoGuo) from oxidation of RNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) from oxidation of DNA are excreted into urine and function as biomarkers for oxidative stress reflecting the modification rate of nucleic acids by oxidation. This study investigates the associations between urinary markers of nucleic acid oxidation and Body Mass Index (BMI), age, sex and cardiometabolic risk factors in children and adolescents with and without obesity.
We studied 543 children and adolescents from an obesity clinic cohort (n = 418) and a population-based cohort (n = 125), all aged 6-18 years. Anthropometrics, urine and blood samples were collected. A validated liquid chromatography-tandem mass spectrometry method was used to measure the nucleic acid oxidation markers.
Compared with the population-based cohort, children and adolescents in the obesity clinic cohort had higher calculated 24-h excretion of 8-oxoGuo (p = 0.045) and 8-oxodG (p = 0.014) adjusted for basal metabolic rate. Both oxidation markers were positively associated with age and female sex (all p < 0.002). In the obesity clinic cohort the RNA oxidation marker 8-oxoGuo correlated with serum insulin (rho = 0.18, p = <.001) and insulin resistance (rho = 0.19, p = <.001).
Childhood obesity associate with higher urinary excretion of nucleic acid oxidation biomarkers, and increase with age throughout childhood, mirroring the obesity- and age-related increase shown in adults. Finally, children with obesity and insulin resistance had higher RNA oxidation markers than children with obesity and no insulin resistance, supporting a possible link between oxidative stress and the pathogenesis of cardiometabolic risk including type 2 diabetes.
氧化应激可能在儿童肥胖和增加的心血管代谢风险中发挥重要作用。RNA 氧化产生的 8-氧代-7,8-二氢鸟苷（8-oxoGuo）和 DNA 氧化产生的 8-氧代-7,8-二脱氧鸟苷（8-oxodG）被排泄到尿液中，作为反映核酸氧化修饰速率的氧化应激生物标志物。本研究调查了肥胖症患儿和青少年以及非肥胖症患儿和青少年尿液中核酸氧化标志物与体重指数（BMI）、年龄、性别和心血管代谢危险因素之间的关联。
我们研究了来自肥胖症诊所队列（n=418）和基于人群的队列（n=125）的 543 名儿童和青少年，年龄均为 6-18 岁。收集了人体测量学、尿液和血液样本。使用经过验证的液相色谱-串联质谱法测量核酸氧化标志物。
与基于人群的队列相比，肥胖症诊所队列的儿童和青少年的 24 小时 8-oxoGuo（p=0.045）和 8-oxodG（p=0.014）排泄量更高，校正基础代谢率后差异仍有统计学意义。这两种氧化标志物均与年龄和女性性别呈正相关（均 p<0.002）。在肥胖症诊所队列中，RNA 氧化标志物 8-oxoGuo 与血清胰岛素（rho=0.18，p<0.001）和胰岛素抵抗（rho=0.19，p<0.001）相关。
儿童肥胖症与尿液中核酸氧化生物标志物排泄增加有关，且随着儿童期年龄的增长而增加，与成年人中肥胖症和年龄相关的增加相吻合。最后，与肥胖症和无胰岛素抵抗的儿童相比，肥胖症和胰岛素抵抗的儿童的 RNA 氧化标志物更高，支持氧化应激与心血管代谢风险（包括 2 型糖尿病）发病机制之间可能存在联系。
