Background Nearly 10 years ago, the World Health Organization reported the increasing prevalence of overweight and obesity worldwide as a challenge for public health due to the associated adverse consequences. Epidemiological studies established a firm relationship between an elevated body mass index and chronic conditions such as diabetes, dyslipidemia, hypertension, heart disease, non-alcoholic fatty liver disease, and some types of cancer. Omic studies demonstrated that microRNA (miRNA) profile changes in tissues correlate with a number of diseases, including obesity. Recent studies showed a remarkable stability of miRNAs also in blood, emphasizing their potential as theranostic agents for a variety of disorders and conditions. A number of miRNAs enriched in homeostasis of obesity and metabolic disorders have been characterized in previous researches. Aim This work was finalized to investigate the differential circulating miRNAs signature in early childhood obesity. Our cross-sectional study analyzed the signature of circulating miRNAs in plasma samples of normal weight (n = 159) and overweight/obese (n = 149) children and adolescents participating to the I.Family study, an EC-funded study finalized to investigate the etiology of overweight, obesity and related disorders and the determinants of food choice, lifestyle, and related health outcomes in children and adolescents of eight European countries (www.ifamilystudy.eu). Results Differences in miRNA signature with respect to anthropometric and biochemical variables were analyzed. A high degree of variability in levels of circulating miRNAs was identified among children from different countries, in line with recent reports supporting the hypothesis that these molecules are likewise affected by environmental and lifestyle factors. A panel of miRNAs differentially expressed in overweight/low-grade obesity children was characterized (miR-551a and miR-501-5p resulted upregulated; miR-10b-5p, miR-191-3p, miR-215-5p, and miR-874-3p resulted downregulated). ROC curves were also constructed for experimentally confirmed miRNAs. Single miRNAs generally exhibited low AUC values with the highest values for miR-874-3p and miR-501-5p which in combination provided an interesting value (AUC = 0.782). Pearson's analysis confirmed that miR-10b-5p, miR-215-5p, miR-501-5p, miR-551a, and miR-874-3p significantly correlated with BMI z-score. Molecular interactions of obesity-associated miRNAs were also predicted by bioinformatics tools. Conclusions Our work showed that several circulating miRNAs are differentially represented in overweight/low-grade obesity children and adolescents. Although causal pathways cannot be firmly inferred, it is conceivable that circulating miRNAs may be new biomarkers of early childhood obesity. Trial registration ISRCTN, ISRCTN62310987. Registered 23/02/2018 - Retrospectively registered.

中文翻译：

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循环 microRNA 与儿童早期肥胖有关：I.Family 研究的结果。

背景 近 10 年前，世界卫生组织报告称，由于相关的不良后果，全球超重和肥胖症的患病率不断上升，这对公共卫生构成了挑战。流行病学研究确定了体重指数升高与糖尿病、血脂异常、高血压、心脏病、非酒精性脂肪肝和某些类型的癌症等慢性病之间的牢固关系。组学研究表明，组织中的 microRNA (miRNA) 谱变化与包括肥胖在内的许多疾病相关。最近的研究表明 miRNA 在血液中也具有显着的稳定性，强调了它们作为治疗各种疾病和病症的治疗剂的潜力。先前的研究已经表征了许多富含肥胖和代谢紊乱稳态的 miRNA。目的 完成这项工作以研究儿童早期肥胖中的差异循环 miRNA 特征。我们的横断面研究分析了参与 I.Family 研究的正常体重 (n = 159) 和超重/肥胖 (n = 149) 儿童和青少年血浆样本中循环 miRNA 的特征，这是一项由 EC 资助的研究，最终确定调查8 个欧洲国家的儿童和青少年的超重、肥胖和相关疾病的病因以及食物选择、生活方式和相关健康结果的决定因素 (www.ifamilystudy.eu)。结果分析了 miRNA 特征在人体测量学和生化变量方面的差异。在来自不同国家的儿童中发现了循环 miRNA 水平的高度可变性，这与最近支持这些分子同样受环境和生活方式因素影响的假设的报告一致。一组在超重/低度肥胖儿童中差异表达的 miRNA 被表征（miR-551a 和 miR-501-5p 导致上调；miR-10b-5p、miR-191-3p、miR-215-5p 和 miR- 874-3p 导致下调）。还为实验证实的 miRNA 构建 ROC 曲线。单个 miRNA 通常表现出较低的 AUC 值，其中 miR-874-3p 和 miR-501-5p 的值最高，两者结合起来提供了一个有趣的值 (AUC = 0.782)。Pearson 的分析证实 miR-10b-5p、miR-215-5p、miR-501-5p、miR-551a 和 miR-874-3p 与 BMI z 评分显着相关。生物信息学工具也预测了肥胖相关 miRNA 的分子相互作用。结论 我们的工作表明，几种循环 miRNA 在超重/低度肥胖儿童和青少年中的表现不同。尽管因果途径无法准确推断，但可以想象，循环 miRNA 可能是儿童早期肥胖的新生物标志物。试用注册 ISRCTN，ISRCTN62310987。2018 年 2 月 23 日注册 - 追溯注册。可以想象，循环 miRNA 可能是儿童早期肥胖的新生物标志物。试用注册 ISRCTN，ISRCTN62310987。2018 年 2 月 23 日注册 - 追溯注册。可以想象，循环 miRNA 可能是儿童早期肥胖的新生物标志物。试用注册 ISRCTN，ISRCTN62310987。2018 年 2 月 23 日注册 - 追溯注册。