Supplementary Material for: Childhood Obesity Is Associated with Changes in the Serum Metabolite Profile

<b><i>Objective: </i></b>The human serum metabolite profile is reflective of metabolic processes, including pathophysiological changes characteristic of diseases. Therefore, investigation of serum metabolite concentrations in obese children might give new insights into biological mechanisms associated with childhood obesity. <b><i>Methods: </i></b>Serum samples of 80 obese and 40 normal-weight children between 6 and 15 years of age were analyzed using a mass spectrometry-based metabolomics approach targeting 163 metabolites. Metabolite concentrations and metabolite ratios were compared between obese and normal-weight children as well as between children of different pubertal stages. <b><i>Results: </i></b>Metabolite concentration profiles of obese children could be distinguished from those of normal-weight children. After correction for multiple testing, we observed 14 metabolites (glutamine, methionine, proline, nine phospholipids, and two acylcarnitines, <i>p </i>&lt; 3.8 × 10^–4) and 69 metabolite ratios (<i>p</i> &lt; 6.0 × 10^–6) to be significantly altered in obese children. The identified metabolite markers are indicative of oxidative stress and of changes in sphingomyelin metabolism, in β-oxidation, and in pathways associated with energy expenditure. In contrast, pubertal stage was not associated with metabolite concentration differences. <b><i>Conclusion: </i></b>Our study shows that childhood obesity influences the composition of the serum metabolome. If replicated in larger studies, the altered metabolites might be considered as potential biomarkers in the generation of new hypotheses on the biological mechanisms behind obesity.

**研究目的**：人体血清代谢物谱可反映机体代谢过程，包括疾病特征性的病理生理变化。因此，针对肥胖儿童血清代谢物浓度开展研究，或可为阐明儿童肥胖相关的生物学机制提供全新视角。

**研究方法**：本研究采用基于质谱的代谢组学（metabolomics）方法，对80名6至15岁肥胖儿童与40名同年龄段正常体重儿童的血清样本进行分析，靶向检测163种代谢物。分别比较肥胖儿童与正常体重儿童，以及不同青春期阶段儿童的代谢物浓度及代谢物比值。

**研究结果**：肥胖儿童的血清代谢物浓度谱可与正常体重儿童相区分。经多重检验校正后，本研究发现肥胖儿童体内共有14种代谢物（谷氨酰胺、甲硫氨酸、脯氨酸、9种磷脂以及2种酰基肉碱（acylcarnitines），*p* < 3.8 × 10^–4）以及69种代谢物比值（*p* < 6.0 × 10^–6）发生显著改变。所鉴定出的代谢物标志物提示机体存在氧化应激（oxidative stress），且鞘磷脂（sphingomyelin）代谢、β氧化（β-oxidation）以及与能量消耗相关的通路均发生异常变化。与之相反，青春期阶段与代谢物浓度差异无显著关联。

**研究结论**：本研究表明，儿童肥胖可影响血清代谢组（metabolome）的组成。若在更大规模研究中得到重复验证，这些发生异常改变的代谢物或可作为潜在生物标志物（biomarker），助力提出关于肥胖背后生物学机制的全新假说。