FTO-dependent m6A methylation mediates gestational diabetes mellitus-induced offspring cardiac senescent hypertrophy and dysfunction.

Fat mass and obesity-associated (FTO) protein plays a critical role in N6-methyladenosine (m6A) demethylation, linked to metabolic disorders such as diabetes and obesity. This study investigates FTO-dependent m6A methylation in fetal programming of cardiac dysfunction due to gestational diabetes mellitus (GDM). Using a Sprague-Dawley rat model of GDM, we observed that GDM exposure repressed FTO, increasing m6A RNA methylation, consequently developing a cardiac hypertrophic dysfunctional phenotype in neonatal offspring. FTO inhibition replicated the effects of GDM, while overexpression of FTO via FTO lentivirus (Lenti-FTO) reversed GDM-induced hypertrophy, cardiac senescence, and dysfunction. These results illuminate the molecular mechanisms by which GDM negatively impacts offspring cardiac health and highlight the potential for targeting FTO-mediated RNA methylation pathways as a therapeutic strategy for GDM-related cardiac issues.