Epigenetic Biomarkers of Transition from Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Phenotype: A Prospective Study

International Journal of Molecular Sciences

Gemma Rojo-Martínez¹  Sergio Valdés¹  Federico Soriguer¹  Andres Gonzalez-Jimenez²  Sonsoles Morcillo³  Teresa María Linares-Pineda³  Carolina Gutiérrez-Repiso³  Francisca Aguilar-Lineros³  Francisco J. Tinahones³ 

[1] Departamento de Endocrinología and Nutrición, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29009 Málaga, Spain;ECAI Bioinformática Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Málaga, Spain;Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Málaga, Spain;

关键词: metabolically healthy obesity;    epigenetic biomarkers;    metabolic syndrome;    DNA methylation;   

DOI  :  10.3390/ijms221910417

来源: DOAJ

【 摘 要 】

Background: Identifying those parameters that could potentially predict the deterioration of metabolically healthy phenotype is a matter of debate. In this field, epigenetics, in particular DNA methylation deserves special attention. Results: The aim of the present study was to analyze the long-term evolution of methylation patterns in a subset of metabolically healthy subjects in order to search for epigenetic markers that could predict the progression to an unhealthy state. Twenty-six CpG sites were significantly differentially methylated, both at baseline and 11-year follow-up. These sites were related to 19 genes or pseudogenes; a more in-depth analysis of the methylation sites of these genes showed that CYP2E1 had 50% of the collected CpG sites differently methylated between stable metabolically healthy obesity (MHO) and unstable MHO, followed by HLA-DRB1 (33%), ZBTB45 (16%), HOOK3 (14%), PLCZ1 (14%), SLC1A1 (12%), MUC2 (12%), ZFPM2 (12.5%) and HLA-DQB2 (8%). Pathway analysis of the selected 26 CpG sites showed enrichment in pathways linked to th1 and th2 activation, antigen presentation, allograft rejection signals and metabolic processes. Higher methylation levels in the cg20707527 (ZFPM2) could have a protective effect against the progression to unstable MHO (OR: 0.21, 95%CI (0.067–0.667), p < 0.0001), whilst higher methylation levels in cg11445109 (CYP2E1) would increase the progression to MUO; OR: 2.72, 95%CI (1.094–6.796), p < 0.0014; respectively). Conclusions: DNA methylation status is associated with the stability/worsening of MHO phenotype. Two potential biomarkers of the transition to an unhealthy state were identified and deserve further investigation (cg20707527 and cg11445109). Moreover, the described differences in methylation could alter immune system-related pathways, highlighting these pathways as therapeutic targets to prevent metabolic deterioration in MHO patients.

【 授权许可】

Unknown