Procyanidins B2-mediated LKB1/AMPK axis in regulating glycolytic metabolic pathways in treatment of obese polycystic ovary syndrome
Objective To investigate the specific mechanism of procyanidins B2(PCB2)in treating obesity-related polycystic ovary syndrome(PCOS).Methods An obesity-induced PCOS rat model was established and treated with different doses of PCB2.Hematoxylin-eosin(HE)staining was used to observe the morphology of the ovarian tissue,enzyme linked immunosorbent assay(ELISA)was used to detect hormone level,actic acid and pyruvic acid levels and adenosine triphosphate(ATP)content,immunohistochemistry(IHC)was used to detect proliferating cell nuclear antigen(PCNA),cystein-asparate protease-3(Caspase-3),liver kinase B1(LKB1)and adenosine 5'-monophosphate-activated protein kinase(AMPK)protein expression and Western blotting(WB)was used to detect apoptotic markers,key rate-limiting enzymes of glucose metabolism,and LKB1/AMPK pathway-related proteins.Results Compared with the control group,the model group showed increased follicular atresia,increased cystic follicles,thinner granular cell layers,and fewer corpora lutea,decreased follicle-stimulating hormone(FSH)and estradiol(E2)(P＜0.01),increased luteinising hormone(LH),testosterone(T),and increased LH/FSH(P＜0.01),decreased lactic acid(LD)and adenosine triphosphate(ATP)(P＜0.001),increased pyruvic acid(P＜0.001),downregulated PCNA,AMPK,and LKB1 expression(P＜0.01),and upregulated Caspase-3 expression(P＜0.01),decreased B-cell lymphoma-2(Bcl-2)protein expression(P＜0.01)and increased Bcl-2-associated X protein(Bax)expression(P＜0.01),significantly decreased lactate dehydrogenase(LDHA)and pyruvate kinase isozyme type M2(PKM2),and LKB1,AMPKα,and phosphorylated-AMPKα(p-AMPKα)protein expression(P＜0.01).Compared with the model group,all doses of PCB2 reversed these changes and alleviated the severity of PCOS(P＜0.05,0.01,0.001).Conclusion PCB2 may treat obesity-related PCOS by regulating the glycolytic metabolic pathway through the LKB1/AMPK axis.
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