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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2024

Open Access 01-12-2024 | Liraglutide | Research

Liraglutide improved the reproductive function of obese mice by upregulating the testicular AC3/cAMP/PKA pathway

Authors: Ruibing Qi, Yuzhen Liang, Jinming Yu, Bing Chen, Jiaqin Jiang, Xingye Wu, Wensheng Lu, Zhengming Li

Published in: Reproductive Biology and Endocrinology | Issue 1/2024

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Abstract

Background

The incidence of male reproductive dysfunction is increasing annually, and many studies have shown that obesity can cause severe harm to male reproductive function. The mechanism of male reproductive dysfunction caused by obesity is unclear, and there is no ideal treatment. Identification of effective therapeutic drugs and elucidation of the molecular mechanism involved in male reproductive health are meaningful. In this study, we investigated the effects of the GLP-1 receptor agonist liraglutide on sex hormones, semen quality, and testicular AC3/cAMP/PKA levels in high-fat-diet-induced obese mice.

Methods

Obese mice and their lean littermates were treated with liraglutide or saline for 12 weeks. Body weight was measured weekly. Fasting blood glucose (FBG) was measured using a blood glucose test strip. The serum levels of insulin (INS), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), free testosterone (F-TESTO), estradiol (E2), and sex hormone binding globulin (SHBG) were detected using ELISA. The sperm morphology and sperm count were observed after Pap staining. The mRNA and protein expression levels of testicular GLP-1R and AC3 were measured by RT-qPCR and Western blot, respectively. Testicular cAMP levels and PKA activity were detected using ELISA.

Results

Liraglutide treatment can decrease body weight, FBG, INS, HOMA-IR, E2 and SHBG levels; increase LH, FSH, T, and F-TESTO levels; increase sperm count; decrease the sperm abnormality rate; and increase GLP-1R and AC3 expression levels and cAMP levels and PKA activity in testicular tissue.

Conclusions

Liraglutide can improve the sex hormone levels and semen quality of obese male mice. In addition to its weight loss effect, liraglutide can improve the reproductive function of obese male mice, which may also be related to the upregulation of AC3/cAMP/PKA pathway in the testis. This work lays the groundwork for future clinical studies.
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Metadata
Title
Liraglutide improved the reproductive function of obese mice by upregulating the testicular AC3/cAMP/PKA pathway
Authors
Ruibing Qi
Yuzhen Liang
Jinming Yu
Bing Chen
Jiaqin Jiang
Xingye Wu
Wensheng Lu
Zhengming Li
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2024
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-024-01202-0

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