DNA methylation of leptin before and after weight loss intervention program among sample of Egyptian obese females: Epigenetic approach in obesity

Background/aim
Obesity phenotype results from interactions between epigenotype and genotype. DNA methylation constitutes the most relevant epigenetic mechanism that regulates gene expression in human cells. Leptin (LEP) has a promoter region that presents CpG (CG dinucleotide repeats) islands which may undergo a methylation process. The DNA methylation process could be influenced by nutrition and alter adipocyte LEP gene expression. This study aimed to investigate whether the LEP gene promoter could be epigenetically modified by dietary weight reduction intervention and whether these changes affect its circulating level which may be involved in regulating the expression of the LEP gene in obesity.
Patient and methods
A total of 82 obese females were prescribed 3 months weight loss program. Fifty-eight women with a mean age of 41.62±10.70 years and a mean baseline BMI of 38.32+ 4.01 kg/m completed this longitudinal follow-up intervention study. Epigenetic mark, baseline and endpoint anthropometric, and laboratory parameters were assessed. Therefore, the methylation of the promoters of the LEP gene, using methylation-specific PCR, and measuring LEP levels before and after the dietary intervention program, and after bisulfite modification were investigated.
Results
After successful weight loss in obese females, Leptin receptor (LEPR) promoter methylation patterns had significantly higher values, and serum LEP levels had significantly lower values compared with before the dietary intervention program (P<0.05). Among the obese females with BMI equal to or more than 40 kg/mthe most increased variable was LEP promoter methylation (↑10.2%), while among the obese females with BMI less than 40 kg/m, it increased by ↑1.7%. Among both groups of obesity, the most decreased variable was LEP (↓94.7% and ↓89.4, respectively).
Conclusion
These results support the assumption that in obesity, there is a link between LEPR methylation and LEP blood levels. The epigenetic profile of LEP gene could be affected by serum LEP via feedback regulation.