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

作者：Deng Guang-hui, Chaofeng Wu, Yunjia Li, Hao Shi, Weichao Zhong, Mukeng Hong, Junjie Li, Jiamin Zhao, Chang Liu, Mengchen Qin, Zhiyun Zeng, Weimin Zhang, Ken Kin Lam Yung, Zhiping Lv, Lei Gao · 发表于：Military Medical Research · 年份：2023 · DOI：10.1186/s40779-023-00487-3 · 被引用次数：25 · 研究领域：Caveolin-1 and cellular processes、Liver Disease Diagnosis and Treatment、Lipid metabolism and disorders

Abstract 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 he...