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Liraglutide Improves PCOS Symptoms in Rats by Targeting FDX1

  • Reproductive Endocrinology: Original Article
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Abstract

Background

Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder characterized by ovulatory disorders, hyperandrogenemia, and polycystic changes in the ovaries. FDX1 is a ferredoxin-reducing protein on human mitochondria that plays an important role in steroid anabolism. Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has recently emerged as a potential therapeutic agent for PCOS. Recent studies have suggested that FDX1 may be associated with the development of PCOS. This study aims to explore the pivotal role of FDX1 in the amelioration of PCOS through liraglutide intervention.

Materials and methods

A PCOS rat model was induced via subcutaneous DHEA injections. Following successful model establishment, the rats were treated with liraglutide combined with metformin, or with each drug individually, over a six-week period. After 6 weeks of treatment, we assessed changes in body weight, fasting blood glucose, sex hormone levels, estrous cycle regularity, ovarian morphology, FDX1 expression in ovarian tissue, and ovarian ROS levels.

Results

PCOS rats exhibited significant increases in body weight and fasting blood glucose levels, disrupted estrous cycles, and polycystic ovarian morphology. FDX1 expression was notably reduced in the ovarian tissues of PCOS rats. Treatment with liraglutide, both alone and in combination with metformin, led to improvements in body weight, fasting blood glucose, sex hormone balance, estrous cycle regularity, ovarian morphology, and ovarian ROS levels. Notably, FDX1 expression was significantly restored in all treatment groups, with the most substantial increase observed in the liraglutide-treated group.

Conclusion

This study suggests that FDX1 could serve as a potential biomarker for elucidating the underlying mechanisms of liraglutide’s therapeutic effects in PCOS management.

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Acknowledgements

We thank Springer Nature for editing the language of a draft of this manuscript (SRHH7N9TR). We also thank the contribution of LONGTAIYINXIN Biotechnology Co., Ltd in this research.

Funding

This work was supported by the Tianjin Natural Science Foundation (Grant No. 21JCYBJC01670).

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Author notes

  1. Shuqing Ji and Hua Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Gynaecology, the Second Hospital of Tianjin Medical University, 300211, Tianjin, China

    Shuqing Ji, Hua Yang, Yuqing Ji, Weifan Wu, Yaping Dong, Hongxia Fu & Fang Wang

  2. NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Institute of Endocrinology, Chu Hsien-I Memorial Hospital, Tianjin Medical University, 300134, Tianjin, China

    Na Tang & Zhimin Hou

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  1. Shuqing Ji
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Contributions

F.W. and Z.H. managed and supervised the research. S.J. and H. Y. completed experiments and wrote the manuscript. Y.J., W.W., Y.D., H.F., N.T. directed the work. All authors read and approved the final manuscript.

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Correspondence to Zhimin Hou or Fang Wang.

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The animal experiment has been reviewed and approved by the Experimental Animal Ethics Committee of Tianjin Medical University Chu Hsien-I Memorial Hospital (DXBYY-IACUC-2022064).

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Ji, S., Yang, H., Ji, Y. et al. Liraglutide Improves PCOS Symptoms in Rats by Targeting FDX1. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01503-0

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