Journal Article

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

García-Ortiz, Humberto, Villafan-Bernal, José Rafael, Carrillo-Ruiz, José Damián, Bastarrachea, Raúl A., Orozco, Lorena, Rodriguez-Ayala, Ernesto, Barajas-Olmos, Francisco, Martínez-Hernández, Angélica, Escalante-Araiza, Fabiola, Contreras-Cubas, Cecilia, Nava-González, Edna J., Centeno-Cruz, Federico, Huerta-Ávila, Eira

2025

Overview

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.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Adipose Tissue - metabolism / Adult / Aged / Asymptomatic / Biosynthesis / Body fat / CpG Islands / Diabetes / Diabetes Mellitus, Type 2 - genetics / Diabetes Mellitus, Type 2 - metabolism / Disease prevention / DNA Methylation / Epigenesis, Genetic / Epigenetics / Fasting - metabolism / Female / Gene expression / Glucose / Human papillomavirus / Humans / Insulin resistance / Insulin Resistance - genetics / Male / Metabolic disorders / Middle Aged / Postprandial Period - genetics / Prediabetic State - genetics / Prediabetic State - metabolism / Proteins / Thyroid gland / Viral infections