Roxadustat alleviates metabolic traits in letrozole-induced PCOS mice

Polycystic ovary syndrome (PCOS) is a highly prevalent disorder, affecting one in eight women across the world. It is commonly accompanied by metabolic syndrome, including obesity, insulin resistance, impaired glucose tolerance and dyslipidemia. Activation of the hypoxia-inducible factor (HIF) pathway is known to alleviate metabolic defects and counteract obesity. Hence, this study utilized a preclinical PCOS mouse model to investigate the effects of chemically induced HIF activation on the metabolic traits of the syndrome. Prepubertal letrozole treatment and C57Bl6/J mice were used to generate a PCOS mouse model. PCOS mice were orally treated with either vehicle or roxadustat for six weeks from age 12 weeks onwards to induce HIF activation. A control group receiving vehicle was also included. After six weeks of treatment, mice were terminated and organs harvested. Liver, skeletal muscle, and white adipose tissues (WAT) were used in RNA sequencing, to investigate differences in gene expression between the experimental groups.