Methylation levels of the <i>LEP, LEPR</i> , and <i>ADIPOQ</i> genes and their association with metabolically healthy obesity

It has been reported that DNA methylation in the epigenetic profile of the genes <i>LEP</i> and <i>ADIPOQ</i> is associated with obesity. To the best of our knowledge, there are no previous reports assessing the methylation of the <i>LEP</i>, <i>LEPR</i>, and <i>ADIPOQ</i> genes in subjects with metabolically healthy obesity (MHO). Therefore, the aim of this study was to determine the association between methylation of the <i>LEP</i>, <i>LEPR</i>, and <i>ADIPOQ</i> genes with the MHO phenotype. Healthy men and women aged 20-55 years of age with a body mass index ≥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 <i>LEP</i> gene was significantly higher than in the MUO group, while the <i>LEPR</i> and <i>ADIPOQ</i> genes did not show differences between the study groups. Finally, the methylation of the <i>LEP</i> gene (OR = 1.67; 95% confidence interval (CI): 1.29-2.16; <i>p</i> < 0.001), but not of <i>LEPR</i> (OR = 0.77; 95% CI: 0.45-1.32; <i>p</i> = 0.350) and <i>ADIPOQ</i> (OR = 1.01; 95% CI: 0.97-1.05; <i>p</i> = 0.411), presented a positive association with the MHO phenotype. In conclusion, the <i>LEP</i> gene hypermethylation is positively associated with the MHO phenotype. In addition, the <i>LEPR</i> gene overexpression was significantly associated with the MHO.