Abstract
Understanding the regulatory mechanisms that affect obesogenic genes expression in newborns is essential for early prevention efforts, but they remain unclear. Our study aimed to explore whether the maternal p-BMI and GWG were associated with regulatory single-locus DNA methylation in selected obesogenic genes. For this purpose, DNA methylation was assayed by Methylation-Sensitive High Resolution Melting (MS-HRM) technique and Sanger allele-bisulfite sequencing in fifty samples of umbilical vein to evaluate glucosamine-6-phosphate deaminase 2 (GNPDA2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), and leptin receptor (LEPR) genes. Correlations between DNA methylation levels and indicators of maternal nutritional status were carried out. Western blotting was used to evaluate protein expression in extracts of the same samples. Results indicated that GNPDA2 and PGC1α genes have the same level of DNA methylation in all samples; however, a differential DNA methylation of LEPR gene promoter was found, correlating it with GWG and this correlation is unaffected by maternal age or unhealthy habits. Furthermore, leptin receptor (Lep-Rb) was upregulated in samples that showed the lowest levels of DNA methylation. This study highlights the association between poor GWG and adjustments on obesogenic genes expression in newborn tissues with potential consequences for development of obesity in the future.
Highlights
Etiology of obesity lies on complex interactions between genetic, epigenetic and environmental factors [1,2,3,4,5]
The current study aimed to explore whether maternal p-BMI and GWG are associated with a single-locus promoter methylation of glucosamine6-phosphate deaminase 2 (GNPDA2), PGC1α and leptin receptor (LEPR) genes and their consequent protein expression in newborns
Qualitative data are available by the presence/absence of consumption habits or complications during pregnancy. p-BMI: pre-pregnancy body mass index; GWG: gestational weight gain; BW: birth weight; BL: birth length; SD: Standard Deviation; CI: Confidence Interval
Summary
Etiology of obesity lies on complex interactions between genetic, epigenetic and environmental factors [1,2,3,4,5]. Developmental programming of obesity may result from altered genetic expression as a fetal adaptive response to adverse intrauterine influences such as maternal diet or nutritional status during pregnancy [8,11,12,13,14]. The study of environmental factors’ effects on gene expression to promote an obesogenic phenotype is still scarce. Epigenetic mechanisms such as DNA methylation have been proposed as mediators of adverse phenotypes [18,19,20]. Preliminary evidence suggests that maternal obesity can have significant effects on neonatal adiposity by altering offspring epigenome-wide DNA methylation [20]. Many articles report DNA methylation variability in offspring tissues linked to obesogenic environments in pregnancy [21,22], it is still uncertain how DNA methylation variability is influenced by interindividual biological variation [23], ethnic and sex composition, and specific organ performance [24,25]
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