Anti-oxidant effect of metformin through AMPK/SIRT1/PGC-1α/SIRT3– independent GPx1 expression in the heart of mice with endometriosis

Rodrigo Felgueiras, Ana C Neto, Ana Catarina Neto, Adriana R Rodrigues, Alexandra Gouveia, Alexandra M Gouveia, Henrique Almeida, Delminda Neves
Hormone molecular biology and clinical investigation · 2022 · vol. 43(4) , pp. 405–414 · doi:10.1515/hmbci-2022-0039 · PMID:35796227 · W4284664137
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study found that metformin increases GPx1 expression in the hearts of endometriosis mice, an effect seemingly independent of the AMPK/SIRT1/PGC-1α/SIRT3 pathway and dependent on the underlying oxidative condition.

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Abstract

OBJECTIVES: Endometriosis is a gynecological disease associated with an imbalance between oxidative species production and anti-oxidative defenses. In women, endometriosis has been reported to associate with increased incidence of cardiovascular events. As such, this study aimed to analyze the oxidation-responsive AMPK/SIRT1/PGC-1α/SIRT3 pathway in the heart of a mouse model of endometriosis. The effect of metformin, an insulin-sensitizing and anti-oxidative drug with already shown positive results in endometriotic tissue was studied. METHODS: Thirty-six female B6CBA/F1 mice were divided into 4 groups (Control-C, Surgery-induced Endometriosis and Metformin-EM (50 mg/kg/day orally administrated for 3 months), Endometriosis-E and Metformin-M). Immunofluorescent labelling of SIRT1 and SIRT3 was performed in the heart tissue. Assessment of expression of AMPKα, SIRT1, PGC-1α, SIRT3, SOD2, and GPx1 was performed by Western Blotting. The quantification of microRNA(miR)-34a, miR-195, miR-217, miR-155 and miR-421, involved in the regulation of expression of SIRT1 and SIRT3, was performed by Real-Time PCR. RESULTS: Data showed an increase in phospho-AMPKα and in GPx1 expression in the EM group when compared to the C group, but not in the total AMPK, SIRT1, PGC-1α, SIRT3 and SOD2, suggesting a GPx1 expression increase independently of the AMPK/SIRT1/PGC-1α/SIRT3 pathway. MicroRNAs, excepting miR-217, showed a consistent trend of increase in the M group. CONCLUSIONS: Our study showed that endometriosis does not significantly affect the expression of the components of the AMPK/SIRT1/PGC-1α/SIRT3 pathway in the heart. However, it indicates that an oxidative condition underlying endometriosis is required for metformin to evidence an increment in the expression of the anti-oxidative enzyme GPx1.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (46)

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