Epigenetic and metabolic signatures in systemic lupus erythematous: The impact of excess body weight on adipose tissue DNA methylation profile

BACKGROUND & AIMS: The interaction between systemic lupus erythematosus (SLE), excess body weight, and epigenetic variation remains poorly understood. This study investigated the association between excess body weight and genome-wide DNA methylation profiles in subcutaneous adipose tissue (SAT) from patients with SLE. METHODS: In this cross-sectional study, 36 premenopausal women with SLE were classified as normal weight (NW,n = 16) or excess body weight (EBW, n = 20). Anthropometric, metabolic, dietary, and physical activity data were collected. Genome-wide DNA methylation in SAT was assessed using the Infinium HumanMethylationEPIC BeadChip. RESULTS: A total of 3783 differentially methylated CpG sites (DMCpGs) were identified between groups, with 1165 hypermethylated and 2618 hypomethylated sites in EBW patients. DMCpGs were enriched in promoter and open sea regions and annotated to immune, inflammatory, and metabolic pathways. DNMT1 expression was higher in EBW patients. CONCLUSIONS: Excess body weight is associated with distinct DNA methylation patterns in SAT from patients with SLE. CLINICALTRIALS: gov Identifier: NCT05097365.