EXPRESS: Methylation levels of the LEP, LEPR, and ADIPOQ genes and their association with metabolically healthy obesity.

It has been reported that DNA methylation in the epigenetic profile of the genes LEP and ADIPOQ is associated with obesity. To the best of our knowledge, there are no previous reports assessing the methylation of the LEP, LEPR, and ADIPOQ genes in subjects with metabolically healthy obesity (MHO). Therefore, the aim of this study was to determine the association between methylation of the LEP, LEPR, and ADIPOQ genes with the MHO phenotype. Healthy men and women aged 20 to 55 years of age with a body mass index (BMI) ≥ 30 kg/m2 were enrolled in a case-control study. Exclusion criteria were pregnancy, alcohol intake, smoking, diabetes, hypertension, hepatic disease, cardiovascular disease, renal disease, thyroid disease, cancer, and/or any type of drug therapy. Individuals with MHO were allocated to the case group while those with metabolically unhealthy obesity (MUO) were assigned to the control group. A total of 78 individuals were enrolled and allocated into the groups with MHO (n=39) or MUO (n=39). In the MHO group, the methylation percentage of the LEP gene was significantly higher than in the MUO group, while the LEPR and ADIPOQ genes did not show differences between the study groups. Finally, the methylation of the LEP gene (OR=1.67; 95%CI:1.29-2.16; p<0.001), but not of LEPR (OR=0.77; 95%CI:0.45-1.32; p=0.350) and ADIPOQ (OR=1.01; 95%CI:0.97-1.05; p=0.411), presented a positive association with the MHO phenotype. In conclusion, the LEP gene hypermethylation is positively associated with the MHO phenotype. Additionally, the LEPR gene overexpression was significantly associated with the MHO.