Effects of Liraglutide on Leptin Promoter Methylation in Ovarian Granulosa Cells of Obese Polycystic Ovary Syndrome Patients

Effects of Liraglutide on Leptin Promoter Methylation in Ovarian Granulosa Cells of Obese Polycystic Ovary Syndrome Patients

Lina Su,¹ Xiaoxia Hao² and Wenhong Lu¹

¹Department of Obstetrics and Gynecology, Shanxi Fenyang Hospital, Fenyang, Shanxi, China
²Department of Obstetrics, Fenyang Hospital, Fenyang, Shanxi, China

Serum leptin (LEP) is elevated in polycystic ovary syndrome (PCOS) patients, especially in obese PCOS patients, which may link to the etiology and development of PCOS. Obesity adversely affects female fertility, and most PCOS patients are obese. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, regulates adipokine production, causes weight loss, and regulates ovarian physiology to improve or manage reproductive status, thus ameliorating obesity and PCOS. This study investigated the impact of liraglutide on LEP promoter methylation levels in ovarian granulosa cells of obese PCOS patients to seek possible potential targets for the clinical treatment. This prospective observational study enrolled 348 PCOS patients with strong fertility desire in our hospital during March 2020-January 2022 who were planned to undergo in vitro fertilization and embryo transfer. Based on the inclusion and exclusion criteria, 207 eligible patients (72 non-obese and 135 obese PCOS patients, 23-37 year-old) were enrolled. Obese PCOS patients [body mass index (BMI) ≥ 25 kg/m²] received liraglutide treatment. Obese PCOS patients exhibited elevated BMI, fasting insulin, fasting blood glucose, HOMA-IR, triglyceride, estradiol, and testosterone levels and reduced high-density lipoprotein cholesterol, luteinizing hormone (LH), LH/follicle-stimulating hormone ratio, and LEP promoter methylation. Liraglutide increases LEP promoter methylation, decreases LEP levels, and affects sex hormone secretion, providing a reference for the investigation of the mechanism of liraglutide in obese PCOS patients. Additionally, weight and fat loss, decreased serum and follicular fluid LEP levels, and increased LEP promoter methylation levels in ovarian granulosa cells may be crucial strategies for treating obese PCOS patients.

Key words —— leptin; liraglutide; methylation; obesity; polycystic ovary syndrome

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Tohoku J. Exp. Med., 2025 May, 266(3), 199-207.

Correspondence: Lina Su, Department of Obstetrics and Gynecology, Shanxi Fenyang Hospital, No.186, Shengli Road, Fenyang, Shanxi 032200, China.

e-mail: Suliinaa@163.com