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La caveolina-1 es crítica para la capacidad de almacenamiento de hierro hepático en el desarrollo de la enfermedad del hígado graso no alcohólico

  • role： Contribute equally, First author同等贡献者, 第一作者
  • Affiliation：

    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

Guang-Hui Deng123,  
  • role： Contribute equally同等贡献者
  • Affiliation：

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

Chao-Feng Wu2,  
  • role： Contribute equally同等贡献者
  • Affiliation：

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

Yun-Jia Li2,  
  • role： Contribute equally同等贡献者
  • Affiliation：

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

Hao Shi2,  
  • Affiliation：

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

Wei-Chao Zhong4,  
  • Affiliation：

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

Mu-Keng Hong2,  
  • Affiliation：

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

Jun-Jie Li2,  
  • Affiliation：

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

Jia-Min Zhao2,  
  • Affiliation：

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

Chang Liu2,  
  • Affiliation：

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

Meng-Chen Qin2,  
  • Affiliation：

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

Zhi-Yun Zeng2,  
  • Affiliation：

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

Wei-Min Zhang1,  
  • Affiliation：

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

Ken Kin Lam Yung5,  
  • Affiliation：

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

Zhi-Ping Lv2,  
  • role： Corresponding author通信作者
  • Affiliation：

    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

  • Email：raygaolei@smu.edu.cn
  • Introduction：*raygaolei@smu.edu.cn
Lei Gao123*

resumen

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.

palabra clave

Caveolin-1;Nonalcoholic fatty liver disease;Iron metabolism;Ferritin;Oxidative stress

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