关键词: 瘦素, 瘦素受体, 阿片-黑素细胞皮质素原, 肥胖, DNA甲基化

Abstract: Objective To investigate the changes in promoter DNA methylation of satiety regulators,the leptin,leptin receptor (leptin-R) and proopiomelanocortin (POMC) in obese children. Methods 45 preschool obese children aged 4 to 6 years,and 45 age-and sex-matched normal-weight children were included in the study.Genomic DNA was extracted from peripheral white blood cells.Bisulfite sequencing-PCR was used to determine the CpG methylation of the leptin promoter (324 bp,-228 to +96),leptin-R promoter (271 bp,-411 to -141) and POMC promoter (275 bp,-341 to -67).Plasma leptin concentrations were measured by enzyme-linked immunosorbent assay. Results Plasma leptin concentration [(21.24±4.02) μg/L] in obese children was higher than that in normal children [(2.95±0.53) μg/L].The mean methylation fraction of 25 CpG sites in the leptin promoter in obese children (0.43±0.13) was lower than that in normal children (0.52±0.15),with significantly reduced methylation fraction in 9 CpG sites.For CpG sites in leptin-R promoter,the methylation fraction was completely demethylated in both obese and normal children.No differences were found in the methylation fraction of CpG sites between the two groups of children. Conclusion Reduced CpG methylation in the leptin promoter may associate with the increased leptin expression and resistance in obese children.

Key words: leptin, leptin receptor, proopiomelanocortin, obesity, DNA methylation