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

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

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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 is a pivotal molecule for predicting and protecting against the development of NAFLD.

Caveolin-1Nonalcoholic fatty liver diseaseIron metabolismFerritinOxidative stress

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

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Department of Gastroenterology,Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510315,China

School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China

Department of Hepatology,Cancer Center,Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510315,China

Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518033,Guangdong,China

Department of Biology,Hong Kong Baptist University,Kowloon Tong,Kowloon,Hong Kong SAR 999077,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaGuangdong Basic and Applied Basic Research FoundationGuangdong Basic and Applied Basic Research FoundationGuangdong Basic and Applied Basic Research FoundationOutstanding Youth Development Scheme project of Southern Medical UniversityYoung Elite Scientists Sponsorship Program by CACMChina Postdoctoral Science Foundation

8207413181774170822609262018B0303060122022A15152201792021A1515011667G6212998702021-QNRC2-B282022M721532

2024

10.1186/s40779-023-00487-3

军事医学研究(英文)

军事医学研究(英文)

CSTPCD
ISSN：2095-7467
年,卷(期)：2024.11(2)
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