首页|Overexpression of Hepcidin Alleviates Steatohepatitisand Fibrosis in a Diet-induced Nonalcoholic Steatohepatitis

Overexpression of Hepcidin Alleviates Steatohepatitisand Fibrosis in a Diet-induced Nonalcoholic Steatohepatitis

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Background and Aims: Iron overload can contribute to the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). Hepcidin (Hamp), which is primarily synthesized in hepatocytes, is a key reg-ulator of iron metabolism. However, the role of Hamp in NASH remains unclear. Therefore, we aimed to elucidate the role of Hamp in the pathophysiology of NASH. Methods:Male mice were fed a choline-deficient L-amino acid-defined (CDAA) diet for 16 weeks to establish the mouse NASH model. A choline-supplemented amino acid-defined (CSAA) diet was used as the control diet. Recombinant adeno-asso-ciated virus genome 2 serotype 8 vector expressing Hamp (rAAV2/8-Hamp) or its negative control (rAAV2/8-NC) was administered intravenously at week 8 of either the CDAA or CSAA diet. Results: rAAV2/8-Hamp treatment markedly decreased liver weight and improved hepatic steatosis in the CDAA-fed mice, accompanied by changes in lipogenesis-related genes and adiponectin expression. Compared with the control group, rAAV2/8-Hamp therapy attenuated liver damage, with mice exhibiting reduced histological NAFLD inflammation and fibrosis, as well as lower levels of liver enzymes. Moreover, α-smooth muscle actin-positive acti-vated hepatic stellate cells (HSCs) and CD68-postive mac-rophages increased in number in the CDAA-fed mice, which was reversed by rAAV2/8-Hamp treatment. Consistent with the in vivo findings, overexpression of Hamp increased adi-ponectin expression in hepatocytes and Hamp treatment inhibited HSC activation. Conclusions: Overexpression of Hamp using rAAV2/8-Hamp robustly attenuated liver stea-tohepatitis, inflammation, and fibrosis in an animal model of NASH, suggesting a potential therapeutic role for Hamp.

Liver fibrosisHepatic stellate cellHepcidinNASHCDAA

Hui Chen、Wenshan Zhao、Xuzhen Yan、Tao Huang、Aiting Yang

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Digestive Department,Beijing Chaoyang Hospital,Capital Medical University,Beijing,China

Experimental and Transla-tional Research Center,Beijing Friendship Hospital,Capital Medical University,Beijing,China

National Clinical Research Center of Digestive Diseases,Beijing,China

Beijing Clinical Medicine Institute,Beijing,China

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国家自然科学基金

81900547

2022

10.14218/JCTH.2021.00289

临床与转化肝病杂志(英文版)

临床与转化肝病杂志(英文版)

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年,卷(期)：2022.10(4)
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