Protective effects of α-ketoglutaric acid on palmitic acid-induced deterioration in sheep endometrial epithelial cells via ferroptosis inhibition

Our results demonstrated that α-KG markedly alleviated PA-induced cytotoxicity. Specifically, α-KG enhanced cell viability, restored proliferative and migratory capacities, promoted cell cycle progression, and attenuated lipid accumulation, DNA damage, histone trimethylation alteration, and apoptosis. Multi-omics profiling, supported by ferroptosis-specific assays, revealed that these cytoprotective effects were predominantly mediated through the suppression of PA-induced ferroptosis. Collectively, our findings provide novel mechanistic insight into the role of α-KG in mitigating lipid-induced cellular stress and establish its therapeutic potential as a metabolic modulator. This study not only advances our understanding of ferroptosis in reproductive cell biology but also opens new avenues for targeted interventions against lipotoxic damage in endometrial tissues.