Abstract
BACKGROUND: Metabolically healthy obesity (MHO) is a considerably controversial concept as it is considered a transitory condition towards the development of different pathologies (type 2 diabetes, insulin resistance, or cardiovascular disease). MHO is closely related to lifestyle and environmental factors. Epigenetics has become an essential biological tool to analyze the link between obesity and metabolic status. The aim of this study was to determine whether MHO status is conditioned by the DNA methylation (DNAm) of several genes related to lipid metabolism (lipoprotein lipase, retinoid X receptor alpha, liver X receptor, stearoyl-CoA desaturase, sterol regulatory element binding factor 1), and inflammation (LEP) in peripheral blood mononuclear cells (PBMCs) from 131 prepubertal subjects with MHO phenotype after lifestyle modifications with personalized Mediterranean diet (MedDiet) combined with a physical activity (PA) program. RESULTS: The DNAm of all studied genes were significantly modified in the population after 12 months of lifestyle modifications (MedDiet and PA). In addition, associations were found between the DNAm studies and BMI, homeostatic model assessment of insulin resistance, monounsaturated fatty acid and polyunsaturated fatty acid, moderate-vigorous PA, fat mass, and adherence to MedDiet. CONCLUSIONS: It was found that DNAm of genes related to lipid metabolism and inflammation are also present in childhood and that this methylation profile can be modified by interventions based on MedDiet and PA.