Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD
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 inv...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223026378 |
| _version_ | 1797388780877905920 |
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| author | Fangzhi Yue Ying Shi Shanyu Wu Lin Xing Dan He Lin Wei Anqi Qiu Ryan Russell Dongmei Zhang |
| author_facet | Fangzhi Yue Ying Shi Shanyu Wu Lin Xing Dan He Lin Wei Anqi Qiu Ryan Russell Dongmei Zhang |
| author_sort | Fangzhi Yue |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T22:45:47Z |
| format | Article |
| id | doaj.art-efed1cb427724fcb8b26c681fc5681b0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T22:45:47Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-efed1cb427724fcb8b26c681fc5681b02023-12-17T06:41:11ZengElsevieriScience2589-00422023-12-012612108560Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLDFangzhi Yue0Ying Shi1Shanyu Wu2Lin Xing3Dan He4Lin Wei5Anqi Qiu6Ryan Russell7Dongmei Zhang8Department of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha 410011, Hunan, ChinaDepartment of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, ChinaDepartment of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, ChinaDepartment of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, ChinaCollege of Pharmacy, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, ChinaDepartment of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, ChinaDepartment of Health and Human Performance, College of Health Professions, University of Texas Rio Grande Valley, Brownsville, TX, USADepartment of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Hunan Engineering Research Center for Obesity and its Metabolic Complications, Xiangya Hospital, Central South University, Changsha 410008, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223026378PharmacologyBiological sciencesBiochemistryPhysiologyCell biology |
| spellingShingle | Fangzhi Yue Ying Shi Shanyu Wu Lin Xing Dan He Lin Wei Anqi Qiu Ryan Russell Dongmei Zhang Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD iScience Pharmacology Biological sciences Biochemistry Physiology Cell biology |
| title | Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD |
| title_full | Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD |
| title_fullStr | Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD |
| title_full_unstemmed | Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD |
| title_short | Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD |
| title_sort | metformin alleviates hepatic iron overload and ferroptosis through ampk ferroportin pathway in hfd induced nafld |
| topic | Pharmacology Biological sciences Biochemistry Physiology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223026378 |
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