Aguilera Concepción M, Gomez-Llorente Carolina, Tofe Inés, Gil-Campos Mercedes, Cañete Ramón, Gil Ángel
Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Centre for Biomedical Research, University of Granada, Armilla, 18100 Granada, Spain.
Unit of Pediatric Endocrinology, Reina Sofia University Hospital, Avda Menéndez Pidal s/n. 14004 Córdoba, Spain.
Int J Mol Sci. 2015 Apr 8;16(4):7723-37. doi: 10.3390/ijms16047723.
Characterization of the genes expressed in adipose tissue (AT) is key to understanding the pathogenesis of obesity and to developing treatments for this condition. Our objective was to compare the gene expression in visceral AT (VAT) between obese and normal-weight prepubertal children. A total of fifteen obese and sixteen normal-weight children undergoing abdominal elective surgery were selected. RNA was extracted from VAT biopsies. Microarray experiments were independently performed for each sample (six obese and five normal-weight samples). Validation by quantitative PCR (qPCR) was performed on an additional 10 obese and 10 normal-weight VAT samples. Of 1276 differentially expressed genes (p < 0.05), 245 were more than two-fold higher in obese children than in normal-weight children. As validated by qPCR, expression was upregulated in genes involved in lipid and amino acid metabolism (CES1, NPRR3 and BHMT2), oxidative stress and extracellular matrix regulation (TNMD and NQO1), adipogenesis (CRYAB and AFF1) and inflammation (ANXA1); by contrast, only CALCRL gene expression was confirmed to be downregulated. In conclusion, this study in prepubertal children demonstrates the up- and down-regulation of genes that encode molecules that were previously proposed to influence the pathogenesis of adulthood obesity, as well as previously unreported dysregulated genes that may be candidate genes in the aetiology of obesity.
脂肪组织（AT）中基因表达的特征对于理解肥胖症的发病机制以及开发针对该病症的治疗方法至关重要。我们的目的是比较肥胖和正常体重的青春期前儿童内脏脂肪组织（VAT）中的基因表达。总共选取了15名肥胖儿童和16名接受腹部择期手术的正常体重儿童。从VAT活检组织中提取RNA。对每个样本（6个肥胖样本和5个正常体重样本）独立进行微阵列实验。对另外10个肥胖和10个正常体重的VAT样本进行定量PCR（qPCR）验证。在1276个差异表达基因（p < 0.05）中，245个基因在肥胖儿童中的表达比正常体重儿童高两倍以上。经qPCR验证，参与脂质和氨基酸代谢（CES1、NPRR3和BHMT2）、氧化应激和细胞外基质调节（TNMD和NQO1）、脂肪生成（CRYAB和AFF1）以及炎症（ANXA1）的基因表达上调；相比之下，只有CALCRL基因表达被证实下调。总之，这项针对青春期前儿童的研究表明，编码先前被认为影响成年肥胖症发病机制的分子的基因存在上调和下调，以及可能是肥胖症病因中候选基因的先前未报道的失调基因。
