METTL3-mediated m6A modification of CD36: Implications for glucose metabolism and inflammatory dysregulation in follicles of polycystic ovary syndrome

[Display omitted] •Aberrant m6A methylation and transcription levels of CD36 were observed in granulosa cells from patients with PCOS.•METTL3 induces glucose uptake and inflammatory disorders by regulating CD36 expression through m6A modification.•Intervention of CD36 improves insulin resistance and ovarian inflammatory disorder in PCOS mice. Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that affects women of reproductive age and is characterized by menstrual irregularities, metabolic imbalances and infertility. The pathogenesis of PCOS is complex and not fully understood, and chronic inflammation and insulin resistance are implicated in its progression. In this study, we investigated the role of m6A methylation, an important epigenetic modification, in the pathogenesis of PCOS. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq), we mapped the m6A methylation profile in granulosa cells from patients with PCOS and identified a significant regulatory effect on gene expression. CD36 is a novel m6A-regulated gene that may facilitate the progression of PCOS. We demonstrated that METTL3, an m6A methyltransferase, modulated CD36 expression and influenced glucose metabolism and inflammatory responses in PCOS. Employing KGN cells as a model of insulin resistance, we observed that CD36 knockdown ameliorated the impaired glucose uptake and significantly reduced the production of pro-inflammatory cytokines. These findings are consistent with the results of CD36 inhibition in a mouse model of PCOS, indicating a role of CD36 in modulating the disease phenotype. Our study delineates a previously unrecognized epigenetic mechanism involving m6A methylation in PCOS, highlighting the potential of targeting the METTL3-CD36 axis as a therapeutic strategy for managing ovarian inflammation and metabolic dysregulation in patients with PCOS.