Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease  

作　　者：Guang-Hui Deng Chao-Feng Wu Yun-Jia Li Hao Shi Wei-Chao Zhong Mu-Keng Hong Jun-Jie Li Jia-Min Zhao Chang Liu Meng-Chen Qin Zhi-Yun Zeng Wei-Min Zhang Ken Kin Lam Yung Zhi-Ping Lv Lei Gao 

机构地区：[1]Department of Gastroenterology,Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510315,China [2]School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China [3]Department of Hepatology,Cancer Center,Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510315,China [4]Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518033,Guangdong,China [5]Department of Biology,Hong Kong Baptist University,Kowloon Tong,Kowloon,Hong Kong SAR 999077,China

出　　处：《Military Medical Research》2024年第2期206-227,共22页军事医学研究（英文版）

基　　金：financially supported by the National Natural Science Foundation of China(82074131,81774170,82260926);the Guangdong Basic and Applied Basic Research Foundation(2018B030306012,2022A1515220179,2021A1515011667);the Outstanding Youth Development Scheme project of Southern Medical University(G621299870);the Young Elite Scientists Sponsorship Program by CACM(2021-QNRC2-B28);the China Postdoctoral Science Foundation(2022M721532).

摘　　要：Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It i

关 键 词：CAVEOLIN-1 Nonalcoholic fatty liver disease Iron metabolism FERRITIN Oxidative stress 

分 类 号：R575.5[医药卫生—消化系统]