Activating transcriptional factor 4 correlated with obesity and insulin resistance in polycystic ovary syndrome

PCOS is a systemic disorder that is commonly characterized by insulin resistance (IR). ATF4 participates in the regulation of energy homeostasis and glucose metabolism, but its role in PCOS remains unclear. In this study, we found that ATF4 was highly expressed in human granulosa cells (hGCs) of PCOS patients with obesity and IR. Thus, we performed Spearman's correlation analysis to further investigate the correlation between ATF4 expression and obesity, lipometabolic disorders, or IR in PCOS. We found that increased ATF4 was an important trigger for lipid accumulation and abnormal insulin signal transduction in PCOS. In cultured KGN cells, insulin positively regulated the mRNA and protein abundance of ATF4. Overexpression of ATF4 significantly impaired insulin-stimulated phosphorylation of AKT. Collectively, our findings provided a novel insight into the molecular mechanisms underlying the occurrence and development of PCOS, implying that ATF4 may be a new molecular target for PCOS therapy.