RT Journal Article
T1 Epigenetic Biomarkers of Transition from Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Phenotype: A Prospective Study
A1 Gutierrez-Repiso, Carolina
A1 Linares-Pineda, Teresa Maria
A1 Gonzalez-Jimenez, Andres
A1 Aguilar-Lineros, Francisca
A1 Valdes, Sergio
A1 Soriguer, Federico
A1 Rojo-Martinez, Gemma
A1 Tinahones, Francisco J.
A1 Morcillo, Sonsoles
K1 Metabolically healthy obesity
K1 Epigenetic biomarkers
K1 Metabolic syndrome
K1 DNA methylation
K1 Immune system
AB 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.
PB MDPI
YR 2021
FD 2021-09-27
LK http://hdl.handle.net/10668/4243
UL http://hdl.handle.net/10668/4243
LA en
NO Gutiérrez-Repiso C, Linares-Pineda TM, Gonzalez-Jimenez A, Aguilar-Lineros F, Valdés S, Soriguer F, et al. Epigenetic Biomarkers of Transition from Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Phenotype: A Prospective Study. Int J Mol Sci. 2021 Sep 27;22(19):10417.
DS RISalud
RD Apr 12, 2025