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Updated: Jan 25, 2026

Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis NASH Resolution
Published on: April 16, 2019
Hepatocellular iNOS protects liver from NASH through Nrf2-dependent activation of HO-1
Yingli Qiao1, Xuehua Li2, Xueli Zhang2
1Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, 317000, China.
Abstract:
Multiple molecular events are involved in non-alcoholic steatohepatitis (NASH). There is no consensus on the role of inducible nitric oxide synthase (iNOS) in the progression of NASH. The present study therefore investigated the role of iNOS in NASH pathogenesis using bone marrow-transplanted iNOS chimeric mice under high-fat diet (HFD) conditions. The chimeric mice were fed a HFD for 16 wk, and primary hepatocytes were stimulated with oleic acid (OA). The molecular mechanisms underlying the role of iNOS in NASH were investigated. Marked hepatic steatosis and injury observed in the HFD mice and OA-stimulated hepatocytes were reduced by hepatocyte-derived iNOS. Mechanistically, iNOS upregulated heme oxygenase 1 (HO-1) by augmenting nuclear factor erythroid 2-related factor 2 (Nrf-2) binding to the HO-1 gene promoter. In conclusion, hepatocyte-derived iNOS may play a protective role against the progression of NASH by upregulating HO-1 through Nrf-2. Upregulation of hepatocellular iNOS may represent a potentially new therapeutic paradigm to combat NASH.
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