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Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD.

Authors :
Yue F
Shi Y
Wu S
Xing L
He D
Wei L
Qiu A
Russell R
Zhang D
Source :
IScience [iScience] 2023 Nov 22; Vol. 26 (12), pp. 108560. Date of Electronic Publication: 2023 Nov 22 (Print Publication: 2023).
Publication Year :
2023

Abstract

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.<br />Competing Interests: All the authors declare no conflicts of interest.<br /> (© 2023 The Author(s).)

Details

Language :
English
ISSN :
2589-0042
Volume :
26
Issue :
12
Database :
MEDLINE
Journal :
IScience
Publication Type :
Academic Journal
Accession number :
38089577
Full Text :
https://doi.org/10.1016/j.isci.2023.108560