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Article

Fasting and Postprandial DNA Methylation Signatures in Adipose Tissue from Asymptomatic Individuals with Metabolic Alterations

by
Fabiola Escalante-Araiza
1,2,
Angélica Martínez-Hernández
1,
Humberto García-Ortiz
1,
Eira Huerta-Ávila
1,
José Rafael Villafan-Bernal
1,3,
Cecilia Contreras-Cubas
1,
Federico Centeno-Cruz
1,
GEMM Family Study
,
Edna J. Nava-González
4,
José Damián Carrillo-Ruiz
5,6,
Ernesto Rodriguez-Ayala
2,
Raúl A. Bastarrachea
7,
Francisco Barajas-Olmos
1,* and
Lorena Orozco
1,*
1
Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City 14610, Mexico
2
Faculty of Health Sciences, Universidad Anáhuac Norte, Mexico City 52786, Mexico
3
Investigador por México, Secretaría de Ciencia, Humanidades, Tecnología e Innovación (SECIHTI), Mexico City 14610, Mexico
4
Facultad de Salud Pública y Nutrición, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico
5
Faculty of Psychology, Universidad Anáhuac Norte, Mexico City 52786, Mexico
6
Stereotactic and Functional Neurosurgery, Hospital General de Mexico, Mexico City 06720, Mexico
7
Population Health Program, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
*
Authors to whom correspondence should be addressed.
Collaborators/Membership of the group/team Name is provided in Acknowledgments.
Int. J. Mol. Sci. 2025, 26(23), 11306; https://doi.org/10.3390/ijms262311306 (registering DOI)
Submission received: 24 October 2025 / Revised: 18 November 2025 / Accepted: 20 November 2025 / Published: 22 November 2025
(This article belongs to the Special Issue Epigenetics of Metabolic Diseases)

Abstract

Cardiometabolic phenotypes such as obesity and impaired insulin action are key determinants of type 2 diabetes (T2D). Growing evidence highlights the postprandial state as a critical window in metabolic regulation, where epigenetic mechanisms, particularly DNA methylation in insulin-sensitive tissues, may play pivotal roles. However, their dynamics across prandial states in subcutaneous adipose tissue (SAT) remain unclear. We analyzed genome-wide DNA methylation in paired fasting and postprandial SAT biopsies from 29 asymptomatic, drug-naïve individuals classified as controls (n = 8), prediabetes n = 9), or T2D (n = 12). Postprandial samples followed a standardized mixed-meal test. DNA methylation was quantified using the Illumina MethylationEPIC array and analyzed through the Chip Analysis Methylation Pipeline (ChAMP) pipeline. Differential methylation was more pronounced postprandially, especially in the T2D group. After adjusting for age and sex, 4599 differentially methylated CpG sites (DMCs) were identified, with increased hypermethylation in T2D. A total of 130 DMCs across 99 genes, including LCLAT1, HLA-C, ZNF714, and HOOK2, were shared by prediabetes and T2D groups. Over-representation analysis revealed 202 enriched pathways related to insulin resistance, AMPK signaling, and immune responses. Additionally, 110 Differentially Methylated Regions (DMRs), including ZNF577 and AGPAT1, were detected. These findings reveal early, prandial-dependent epigenetic alterations in SAT that precede overt dysglycemia, offering insights into personalized prevention in T2D.
Keywords: subcutaneous adipose tissue; postprandial state; mixed meal challenge; obesity; prediabetes; type 2 diabetes; epigenetic biomarkers; differential DNA methylation subcutaneous adipose tissue; postprandial state; mixed meal challenge; obesity; prediabetes; type 2 diabetes; epigenetic biomarkers; differential DNA methylation

Share and Cite

MDPI and ACS Style

Escalante-Araiza, F.; Martínez-Hernández, A.; García-Ortiz, H.; Huerta-Ávila, E.; Villafan-Bernal, J.R.; Contreras-Cubas, C.; Centeno-Cruz, F.; GEMM Family Study; Nava-González, E.J.; Carrillo-Ruiz, J.D.; et al. Fasting and Postprandial DNA Methylation Signatures in Adipose Tissue from Asymptomatic Individuals with Metabolic Alterations. Int. J. Mol. Sci. 2025, 26, 11306. https://doi.org/10.3390/ijms262311306

AMA Style

Escalante-Araiza F, Martínez-Hernández A, García-Ortiz H, Huerta-Ávila E, Villafan-Bernal JR, Contreras-Cubas C, Centeno-Cruz F, GEMM Family Study, Nava-González EJ, Carrillo-Ruiz JD, et al. Fasting and Postprandial DNA Methylation Signatures in Adipose Tissue from Asymptomatic Individuals with Metabolic Alterations. International Journal of Molecular Sciences. 2025; 26(23):11306. https://doi.org/10.3390/ijms262311306

Chicago/Turabian Style

Escalante-Araiza, Fabiola, Angélica Martínez-Hernández, Humberto García-Ortiz, Eira Huerta-Ávila, José Rafael Villafan-Bernal, Cecilia Contreras-Cubas, Federico Centeno-Cruz, GEMM Family Study, Edna J. Nava-González, José Damián Carrillo-Ruiz, and et al. 2025. "Fasting and Postprandial DNA Methylation Signatures in Adipose Tissue from Asymptomatic Individuals with Metabolic Alterations" International Journal of Molecular Sciences 26, no. 23: 11306. https://doi.org/10.3390/ijms262311306

APA Style

Escalante-Araiza, F., Martínez-Hernández, A., García-Ortiz, H., Huerta-Ávila, E., Villafan-Bernal, J. R., Contreras-Cubas, C., Centeno-Cruz, F., GEMM Family Study, Nava-González, E. J., Carrillo-Ruiz, J. D., Rodriguez-Ayala, E., Bastarrachea, R. A., Barajas-Olmos, F., & Orozco, L. (2025). Fasting and Postprandial DNA Methylation Signatures in Adipose Tissue from Asymptomatic Individuals with Metabolic Alterations. International Journal of Molecular Sciences, 26(23), 11306. https://doi.org/10.3390/ijms262311306

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