Differential gene expression in omental adipose tissue from obese children

Characterization of genes associated with adipose tissue is key to understanding the pathogenesis of obesity and developing treatments for this disorder. Differential gene expression in the adipose tissue has been described in adulthood but none studies have been developed on childhood. The purpose of this study was to compare gene expression in omental adipose tissue from obese prepubertal and normal weight children. We selected 5 obese (BMI adjusted for age and sex z score >2) and 6 normal weight children. RNA was extracted from omental adipose tissue biopsies and cRNA was hybridizated on the human genome U133 Plus 2.0 Arrays (Affymetrix®). Microarray experiments were performed for each sample, and selected group of gene expression values were confirmed with real-time RT-PCR in 10 obese and 10 normal weigth prepubertal children. 1276 genes were found to be differentially expressed at P<0.05. Of those differential genes, 201 were upregulated (Fc>2) and 42 were downregulated (Fc<-2). Genes involved in metabolic and signalling pathways were altered in childhood obesity. Keywords: disease state analysis Adipose tissue and blood samples were obtained from 27 children, 14 obese (BMI adjusted for age and sex z score > 2) and 13 non obese undergoing appendix surgery. About 400 mg of adipose tissue was taken and immediately immersed in RNAlater solution and stored at -80°C for gene expression analysis. Informed consent was obtained from all patients after the nature of the study was explained, and the experimental design was approved, from an ethical and scientific standpoint, by the Hospital’s Ethical Committee responsible for research.

阐明与脂肪组织相关的基因特征，是解析肥胖发病机制、开发该疾病治疗手段的核心关键。成人脂肪组织的差异基因表达谱已有相关报道，但针对儿童群体的相关研究仍属空白。
本研究旨在对比肥胖青春前期儿童与正常体重儿童的网膜脂肪组织基因表达差异。本研究纳入5名肥胖（按年龄和性别校正的身体质量指数（BMI）z评分＞2）儿童及6名正常体重儿童。
从网膜脂肪组织活检样本中提取总RNA，将合成的互补RNA（cRNA）与人类基因组U133 Plus 2.0芯片（Affymetrix®）进行杂交。对所有样本均开展芯片实验，并选取部分基因表达量通过实时荧光定量逆转录PCR（real-time RT-PCR）在另外10名肥胖及10名正常体重的青春前期儿童样本中进行验证。
经筛选，共有1276个基因在两组间呈现显著差异表达（P＜0.05）；其中201个基因表达上调（倍数变化Fc＞2），42个基因表达下调（Fc＜-2）。儿童肥胖患者体内，参与代谢通路与信号通路的基因表达均发生显著改变。
关键词：疾病状态分析
本研究从27名儿童体内采集脂肪组织与血液样本，其中14名为肥胖儿童（按年龄和性别校正的BMI z评分＞2），其余13名为接受阑尾切除术的非肥胖儿童。采集约400mg脂肪组织后，立即将其浸没于RNAlater保存液中，并于-80℃低温保存，用于后续基因表达分析。
所有受试者均在知晓研究内容后签署知情同意书；本研究的实验设计已通过医院科研伦理委员会的伦理与学术审核。