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Liraglutide improved the reproductive function of obese mice by upregulating the testicular AC3/cAMP/PKA pathway
Ruibing Qi1,2, Yuzhen Liang3, Jinming Yu1
1Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China.
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.
Insights
The GLP-1 receptor agonist liraglutide improves male reproductive function in obese mice by enhancing sex hormones and semen quality. This effect may involve the testicular AC3/cAMP/PKA pathway, offering hope for future treatments.
Area of Science:
- Reproductive Endocrinology
- Metabolic Syndrome
- Pharmacology
Background:
- Obesity is linked to increasing male reproductive dysfunction, with unclear mechanisms and limited treatments.
- Investigating therapeutic agents for obesity-induced male infertility is crucial for public health.
- The role of GLP-1 receptor agonists in male reproductive health requires further elucidation.
Purpose of the Study:
- To evaluate the efficacy of liraglutide, a GLP-1 receptor agonist, in ameliorating reproductive impairments in diet-induced obese mice.
- To investigate the impact of liraglutide on sex hormone profiles and semen parameters in obese male mice.
- To explore the potential molecular mechanisms, including testicular AC3/cAMP/PKA pathway modulation, underlying liraglutide's effects.
Main Methods:
- Obese and lean mice were administered liraglutide or saline for 12 weeks, monitoring body weight and fasting blood glucose.
- Serum levels of key hormones (LH, FSH, testosterone, estradiol) and metabolic markers (insulin, HOMA-IR) were quantified via ELISA.
- Semen quality was assessed through sperm count and morphology analysis, alongside testicular gene and protein expression of GLP-1R and AC3, and cAMP/PKA activity.
Main Results:
- Liraglutide treatment significantly reduced body weight, fasting blood glucose, insulin, and HOMA-IR in obese mice.
- Liraglutide administration restored normal levels of luteinizing hormone, follicle-stimulating hormone, testosterone, and free testosterone.
- Semen quality improved with increased sperm count, reduced abnormality rates, and enhanced testicular GLP-1R, AC3, cAMP, and PKA activity.
Conclusions:
- Liraglutide effectively improves sex hormone profiles and semen quality in obese male mice, independent of weight loss.
- The beneficial effects of liraglutide on male reproductive function may be mediated by the upregulation of the testicular AC3/cAMP/PKA pathway.
- This study provides a foundation for exploring liraglutide as a therapeutic option for male reproductive dysfunction associated with obesity.
