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Semaglutide Alleviates Ovary Inflammation via the AMPK/SIRT1/NF‑κB Signaling Pathway in Polycystic Ovary Syndrome Mice.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2024 Sep 04; Vol. 18, pp. 3925-3938. Date of Electronic Publication: 2024 Sep 04 (Print Publication: 2024). - Publication Year :
- 2024
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Abstract
- Background: GLP-1 receptor agonists (GLP-1 RA) have been proven to treat several metabolic diseases; however, the effects of GLP-1 RA on polycystic ovary syndrome (PCOS) remain unclear. Here, we aimed to investigate whether semaglutide, a novel GLP-1 RA, could alleviate ovarian inflammation in PCOS mice.<br />Methods: Female C57BL/6J mice were subcutaneously injected with dehydroepiandrosterone for 21 days to establish the PCOS model. Then the mice were randomly divided into three groups: PCOS group (n = 6), S-0.42 group (semaglutide 0.42 mg/kg/w, n = 6), and S-0.84 group (semaglutide 0.84 mg/kg/w, n = 6). The remaining six mice were used as controls (NC). After 28 days of intervention, serum sex hormones and inflammatory cytokine levels were measured. Hematoxylin and eosin staining was used to observe the ovarian morphology. Immunohistochemical staining was used to detect the relative expression of CYP19A1, TNF-α, IL-6, IL-1β, and NF-κB in ovaries. CYP17A1 and StAR were detected using immunofluorescence staining. Finally, the relative expressions of AMPK, pAMPK, SIRT1, NF-κB, IκBα, pIκBα, TNF-α, IL-6, and IL-1β were measured using Western blotting.<br />Results: First, after intervention with semaglutide, the weight of the mice decreased, insulin resistance improved, and the estrous cycle returned to normal. Serum testosterone and IL-1β levels decreased significantly, whereas estradiol and progestin levels increased significantly. Follicular cystic dilation significantly improved. The expression of TNF-α, IL-6, IL-1β, NF-κB, CYP17A1, and StAR in the ovary was significantly downregulated, whereas CYP19A1 expression was upregulated after the intervention. Finally, we confirmed that semaglutide alleviates ovarian tissue inflammation and improves PCOS through the AMPK/SIRT1/NF-κB signaling pathway.<br />Conclusion: Semaglutide alleviates ovarian inflammation via the AMPK/SIRT1/NF‑κB signaling pathway in PCOS mice.<br />Competing Interests: The authors declare that they have no conflicts of interest in this work.<br /> (© 2024 Liu et al.)
- Subjects :
- Animals
Female
Mice
AMP-Activated Protein Kinases metabolism
Disease Models, Animal
Mice, Inbred C57BL
NF-kappa B metabolism
Ovary drug effects
Ovary pathology
Ovary metabolism
Sirtuin 1 metabolism
Glucagon-Like Peptides pharmacology
Inflammation drug therapy
Inflammation metabolism
Polycystic Ovary Syndrome drug therapy
Polycystic Ovary Syndrome metabolism
Polycystic Ovary Syndrome pathology
Signal Transduction drug effects
Glucagon-Like Peptide-1 Receptor Agonists pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 18
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 39247793
- Full Text :
- https://doi.org/10.2147/DDDT.S484531