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

作者全名："Yue, Fangzhi; Shi, Ying; Wu, Shanyu; Xing, Lin; He, Dan; Wei, Lin; Qiu, Anqi; Russell, Ryan; Zhang, Dongmei"

作者地址："[Yue, Fangzhi; Shi, Ying; Wu, Shanyu; Xing, Lin; Wei, Lin; Qiu, Anqi; Zhang, Dongmei] Cent South Univ, Xiangya Hosp, Dept Endocrinol, Changsha 410008, Hunan, Peoples R China; [Yue, Fangzhi] Cent South Univ, Key Lab Diabet Immunol, Minist Educ, Changsha 410011, Hunan, Peoples R China; [He, Dan] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Russell, Ryan] Univ Texas Rio Grande Valley, Coll Hlth Profess, Dept Hlth & Human Performance, Brownsville, TX USA; [Zhang, Dongmei] Cent South Univ, Xiangya Hosp, Hunan Engn Res Ctr Obes & Its Metab Complicat, Changsha 410008, Peoples R China"

通信作者："Zhang, DM (通讯作者)，Cent South Univ, Xiangya Hosp, Dept Endocrinol, Changsha 410008, Hunan, Peoples R China.; Zhang, DM (通讯作者)，Cent South Univ, Xiangya Hosp, Hunan Engn Res Ctr Obes & Its Metab Complicat, Changsha 410008, Peoples R China."

来源：ISCIENCE

ESI学科分类：　

WOS号：WOS:001128903400001

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：26

期号：12

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："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."

基金机构："National Natural Science Foundation of China [82070884]; Natural Science Foundation of Hunan Province [2021JJ31123]; Key laboratory of diabetes immunology, ministry of education [DKME202213]"

基金资助正文："ACKNOWLEDGMENTS This research was supported by the National Natural Science Foundation of China (NO. 82070884) , Natural Science Foundation of Hunan Province (No. 2021JJ31123) , and Key laboratory of diabetes immunology, ministry of education (No. DKME202213) ."