Obesity induced alterations in redox homeostasis and oxidative stress are present from an early age

ObjectivesOxidative stress and inflammation have been postulated as underlying mechanisms for the development of obesity-related insulin resistance. This association however, remains elusive especially in childhood. We sought to investigate this relation by measuring oxidative stress and antioxidant response biomarkers, before and during an oral glucose tolerance test (OGTT), in different biological samples from obese children.Subjects24 children were recruited for the study, (18 obese and 6 controls). After OGTT, the obese group was subdivided in two, according to whether or not carbohydrate metabolic impairment (Ob.IR+, Ob.IR-; respectively) was found. Different biomarkers were analyzed after fasting (T = 0) and during an OGTT (T = 60 and 120 min). Lipoperoxides were measured in plasma, erythrocytes, and urine; while advanced glycation end products were determined in plasma, and redox status (GSH/GSSG ratio) in erythrocytes.ResultsWe found marked differences in the characterization of the oxidative status in urine and erythrocytes, and in the dynamics of the antioxidant response during OGTT. Specifically, Ob.IR+ children show increased oxidative stress, deficient antioxidant response and a significant imbalance in redox status, in comparison to controls and Ob.IR- children.ConclusionObese children with insulin resistance show increased levels of oxidative stress biomarkers, and a stunted antioxidant response to an OGTT leading to increased oxidative stress after a single glucose load, as detected in erythrocytes, but not in plasma. We propose erythrocytes as sensors of early and acute changes in oxidative stress associated with insulin resistance in childhood obesity. This is a pilot study, performed with a limited sample size, so data should be interpreted with caution until reproduced.

研究目的
氧化应激与炎症被假定为肥胖相关性胰岛素抵抗发生的潜在机制。然而该关联仍未明晰，在儿童群体中尤为突出。本研究旨在通过检测肥胖儿童不同生物样本在口服葡萄糖耐量试验（Oral Glucose Tolerance Test, OGTT）前后及试验过程中的氧化应激与抗氧化应答生物标志物，探究二者的内在关联。

研究对象
本研究共招募24名儿童，其中肥胖组18名，对照组6名。完成OGTT后，根据糖代谢受损情况将肥胖组划分为两个亚组：合并糖代谢异常者（Ob.IR+）与糖代谢正常者（Ob.IR-）。分别于空腹状态（T=0）、OGTT进行后60分钟（T=60）及120分钟（T=120）采集样本，检测多项生物标志物：血浆、红细胞及尿液中的脂质过氧化物；血浆中的晚期糖基化终末产物（advanced glycation end products）；以及红细胞内的氧化还原状态（谷胱甘肽/氧化型谷胱甘肽比值，GSH/GSSG ratio）。

研究结果
本研究发现，尿液与红细胞内的氧化状态特征，以及OGTT过程中抗氧化应答的动态变化均存在显著差异。具体而言，与对照组及Ob.IR-亚组儿童相比，Ob.IR+亚组儿童表现为氧化应激水平升高、抗氧化应答缺陷，且氧化还原状态存在显著失衡。

研究结论
合并胰岛素抵抗的肥胖儿童，其氧化应激生物标志物水平升高，且对OGTT的抗氧化应答受损，单次葡萄糖负荷后可引发红细胞内氧化应激水平升高，但血浆中未检测到此变化。本研究提出红细胞可作为儿童肥胖合并胰岛素抵抗相关氧化应激早期及急性变化的感知标志物。本研究为预试验，样本量有限，相关数据需谨慎解读，待后续研究重复验证后方可采信。