Work

Metformin-mediated intestinal AMPK activation ameliorates PCOS through gut microbiota modulation and metabolic pathways

Year: 2025

Type: article

Abstract: Introduction: Polycystic ovary syndrome (PCOS) is a complex disorder characterized by metabolic and ovulatory dysfunctions, often associated with an imbalance in gut microbiota. Despite current treatments, effective management strategies targeting underlying mechanisms remain limited. Methods: In this study, we used a rat model of PCOS induced by letrozole and a high-fat diet. The effect of intestinal AMP-activated protein kinase (AMPK) activation was evaluated through metformin administration, the most commonly used AMPK activator. We analyzed metabolic parameters, ovulatory functions, gut microbiota composition, and serum levels of Indole-3-carboxaldehyde (I3A), a metabolite involved in inflammation and apoptosis regulation. Results: Metformin treatment significantly reversed metabolic disorders and restored ovulatory functions in PCOS rats. Moreover, metformin treatment led to notable improvements in gut microbiota composition and an increase in serum I3A levels, which have been shown to mitigate inflammation and apoptosis. Discussion: This study highlights the therapeutic potential of targeting intestinal AMPK in managing PCOS. By improving both metabolic and reproductive health, activation of AMPK may offer a promising approach for restoring physiological balance in PCOS patients.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2025.1526109

Authors: Yating Xu, Li Ning, Yu Si, Xiu Li, Ruyue Wang, Qingling Ren

Institution: Nanjing University of Chinese Medicine

Language: English

Topic: Ovarian function and disorders

Subfield: Reproductive Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801