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Related Experiment Video

Updated: Jun 13, 2025

Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
04:49

Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome

Published on: July 5, 2024

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Roxadustat alleviates metabolic traits in letrozole-induced PCOS mice.

Nikke Virtanen1, Ulla Saarela2, Mikko Karpale3

  • 1Department of Obstetrics and Gynecology, Medical Research Centre, Research Unit of Clinical Medicine, University of Oulu, Oulu University Hospital, Oulu, Finland; Research Unit of Extracellular Matrix and Hypoxia, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland.

Biochemical Pharmacology
|September 8, 2024
PubMed
Summary

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Effect of Roxadustat on Cardiometabolism in Healthy Individuals (ROXACardioMeta): Protocol for a Double-Blind, Placebo-Controlled and Randomised Cross-Over Trial.

Methods and protocols·2026

Hypoxia-inducible factor (HIF) activation via roxadustat improved glucose tolerance and insulin resistance in a preclinical polycystic ovary syndrome (PCOS) mouse model. This suggests HIF pathway activation as a potential therapeutic strategy for PCOS metabolic dysfunction.

Area of Science:

  • Endocrinology
  • Metabolic Disorders
  • Pharmacology

Background:

  • Polycystic ovary syndrome (PCOS) is a common endocrine disorder frequently associated with metabolic syndrome.
  • The hypoxia-inducible factor (HIF) pathway is recognized for its role in mitigating metabolic abnormalities.

Purpose of the Study:

  • To investigate the impact of chemically induced HIF activation on the metabolic characteristics of a preclinical polycystic ovary syndrome (PCOS) mouse model.
  • To evaluate the therapeutic potential of roxadustat, a HIF activator, in ameliorating PCOS-related metabolic defects.

Main Methods:

  • A PCOS mouse model was established using prepubertal letrozole treatment in C57Bl6/J mice.
  • PCOS mice received oral treatment with either vehicle or roxadustat for six weeks to induce HIF activation.
Keywords:
HIF prolyl 4-hydroxylaseLetrozoleMetabolismPCOSPrepubertalRoxadustat

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  • Metabolic parameters, including glucose tolerance, insulin resistance, blood lipids, and tissue histology, were assessed.

    • Main Results:

    • PCOS mice exhibited impaired glucose tolerance, insulin resistance, elevated blood lipids, and reduced muscle glycogen.
    • Roxadustat treatment significantly improved glucose tolerance (27% AUC reduction) and insulin resistance (46% HOMA-IR reduction) compared to vehicle controls.
    • While roxadustat did not alter body weight or affect WAT/liver histology, it increased uncoupling protein 1 (UCP1) expression in WAT, suggesting potential WAT browning.

    Conclusions:

    • Chemically induced HIF activation with roxadustat effectively ameliorates key metabolic dysfunctions in a PCOS mouse model.
    • HIF pathway activation demonstrates promise as a therapeutic approach for managing metabolic disturbances in PCOS.
    • Roxadustat-induced WAT browning, indicated by UCP1 upregulation, may contribute to the observed metabolic improvements in PCOS.