Abstract
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.
Highlights
Childhood obesity is one of the most important public health problems of the 21st century, affecting both developed and developing countries
To the best of our knowledge, this study reports the first investigation of prepubertal children in which obesity-induced gene expression changes have been globally analysed in visceral adipose tissue (VAT) using genome wide microarrays, providing valuable new insight into the pathology of early-onset human obesity
Our data demonstrate that the VAT of obese children exhibits a gene expression profile that differs from their normal-weight peers
Summary
Childhood obesity is one of the most important public health problems of the 21st century, affecting both developed and developing countries. Most microarray-based expression studies that have been published to date have been performed on obese adults and have compared the gene expression profiles in VAT vs SAT [8,9,10]. Regarding studies performed in children, only one has compared the gene expression data for SAT and VAT [13]. Studies in prepubertal children can offer important insight into the genetic basis of obesity because excess weight during the growing years constitutes a major risk for being overweight or obese during adult life. Our primary objective was to determine the gene expression profile of fat depots in obese and normal-weight prepubertal children. To the best of our knowledge, this study is the first to analyse whole genome expression in VAT from prepubertal obese children and to compare it with that in normal-weight children. Expression profile of VAT in prepubertal children, by using DNA microarrays and subsequently to validate these findings with quantitative PCR (qPCR) methods
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