Document Type
Article
Publication Date
12-15-2023
Abstract
Highlights
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Metformin alleviates HIO and ferroptosis in HFD-induced NAFLD
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FPN is involved in the molecular mechanism of metformin on HIO in HFD-induced NAFLD
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Metformin upregulates FPN expression by reducing lysosomal ubiquitination degradation
Summary
Metformin prevents progression of non-alcoholic fatty liver disease (NAFLD). However, the potential mechanism is not entirely understood. Ferroptosis, a recently recognized nonapoptotic form of regulated cell death, has been reported to be involved in the pathogenesis of NAFLD. Here, we investigated the effects of metformin on ferroptosis and its potential mechanism in NAFLD. We found that metformin prevented the progression of NAFLD, and alleviated hepatic iron overload (HIO), ferroptosis and upregulated ferroportin (FPN) expression in vivo and in vitro. Mechanically, metformin reduced the lysosomal degradation pathway of FPN through activation AMPK, thus upregulated the expression of FPN protein, alleviated HIO and ferroptosis, and prevented progression of NAFLD. These findings discover a mechanism of metformin, suggesting that targeting FPN may have the therapeutic potential for treating NAFLD and related disorders.
Recommended Citation
Yue, Fangzhi, et al. "Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD." Iscience 26.12 (2023): 108560. https://doi.org/10.1016/j.isci.2023.108560
DOI
10.1016/j.isci.2023.108560
Comments
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