2026-08-12T20:37:31Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/184712024-11-28T15:23:16Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
Gutiérrez-Repiso, Carolina
author
Linares-Pineda, Teresa María
author
Gonzalez-Jimenez, Andres
author
Aguilar-Lineros, Francisca
author
Valdés, Sergio
author
Soriguer, Federico
author
Rojo-Martínez, Gemma
author
Tinahones, Francisco J.
author
Morcillo, Sonsoles
authoraffiliation
[Gutiérrez-Repiso,C; Linares-Pineda,TM; Aguilar-Lineros,F; Tinahones,FJ; Morcillo,S] Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Gutiérrez-Repiso,C; Tinahones,FJ; Morcillo,S] Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. [Gonzalez-Jimenez,A] ECAI Bioinformática Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Valdés,S; Soriguer,F; Rojo-Martínez,G] Departamento de Endocrinología and Nutrición, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Valdés,S; Soriguer,F; Rojo-Martínez,G] Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. [Tinahones,FJ] Departamento de Medicina y Dermatología, Universidad de Málaga, Málaga, Spain.
2024-02-19T15:31:09Z
2024-02-19T15:31:09Z
2021-09-27
10.3390/ijms221910417
1422-0067
International Journal of Molecular Sciences
http://hdl.handle.net/10668/4243
34638758
http://hdl.handle.net/20.500.12105/18471
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.
eng
Metabolically healthy obesity
Epigenetic biomarkers
Metabolic syndrome
DNA methylation
Immune system
Obesidad metabólica benigna
Biomarcadores
Síndrome metabólico
Metilación de ADN
Sistema inmunológico
Epigenetic Biomarkers of Transition from Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Phenotype: A Prospective Study
research article