Semaglutide Alleviates Ovary Inflammation via the AMPK/SIRT1/NFκB Signaling Pathway in Polycystic Ovary Syndrome Mice.
Drug Des Devel Ther
; 18: 3925-3938, 2024.
Article
en En
| MEDLINE
| ID: mdl-39247793
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.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-1ß, 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-1ß were measured using Western blotting.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-1ß levels decreased significantly, whereas estradiol and progestin levels increased significantly. Follicular cystic dilation significantly improved. The expression of TNF-α, IL-6, IL-1ß, 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.Conclusion:
Semaglutide alleviates ovarian inflammation via the AMPK/SIRT1/NFκB signaling pathway in PCOS mice.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome del Ovario Poliquístico
/
Transducción de Señal
/
Péptidos Similares al Glucagón
/
Agonistas Receptor de Péptidos Similares al Glucagón
/
Inflamación
Límite:
Animals
Idioma:
En
Revista:
Drug Des Devel Ther
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Nueva Zelanda