ArticleThe Journal of biological chemistry2011
Hepatitis B virus X protein regulates hepatic glucose homeostasis via activation of inducible nitric oxide synthase.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Systematic review and meta-analysis:Frontiers in pharmacology · 2024Pooled it
- Hepatitis B virus protein X promotes survival and loss of hepatocyte identity in a differentiated human liver organoid system.Cell death and differentiation · 2026Article
- Beyond diabetes and obesity: GLP-1 receptor agonists as multifunctional therapeutics across the steatotic liver disease spectrum.Frontiers in pharmacology · 2026Review
- The bittersweet link between glucose metabolism, cellular microenvironment and viral infection.Virulence · 2025Review
- HBV and host metabolic crosstalk: Reprogramming pathways for viral replication and pathogenesis.Virologica Sinica · 2025Review
- Potential Protective Effect of Hepatitis B Immunity Against Diabetes Mellitus: A Retrospective Propensity-Matched Cohort Study.Diagnostics (Basel, Switzerland) · 2025Article
- Metabolic hijacking styles: a review of how viral life cycles dictate glucose metabolism reprogramming.Frontiers in microbiology · 2025Review
- Prevalence and Risk Factors of Type 2 Diabetes Mellitus Among Hepatitis B Virus Patients: A Large Retrospective Cohort Study.International journal of medical sciences · 2025Article
- Norovirus NS1/2 protein increases glutaminolysis for efficient viral replication.PLoS pathogens · 2024Article
- Hepatic macrophage niche: a bridge between HBV-mediated metabolic changes with intrahepatic inflammation.Frontiers in immunology · 2024Review
- Host and HBV Interactions and Their Potential Impact on Clinical Outcomes.Pathogens (Basel, Switzerland) · 2023Review
- Article
- O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an NSignal transduction and targeted therapy · 2023Article
- Small Hepatitis B Virus Surface Antigen Promotes Hepatic Gluconeogenesis via Enhancing Glucagon/cAMP/Protein Kinase A/CREB Signaling.Journal of virology · 2022Article
- Review
- Transcriptomic Analysis of Livers of Inactive Carriers of Hepatitis B Virus With Distinct Expression of Hepatitis B Surface Antigen.The Journal of infectious diseases · 2022Article
- Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences.International journal of molecular sciences · 2022Review
- Review
- mTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication.Virologica Sinica · 2021Review
- Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
Abstract
Dysregulation of liver functions leads to insulin resistance causing type 2 diabetes mellitus and is often found in chronic liver diseases. However, the mechanisms of hepatic dysfunction leading to hepatic metabolic disorder are still poorly understood in chronic liver diseases. The current work investigated the role of hepatitis B virus X protein (HBx) in regulating glucose metabolism. We studied HBx-overexpressing (HBxTg) mice and HBxTg mice lacking inducible nitric oxide synthase (iNOS). Here we show that gene expressions of the key gluconeogenic enzymes were significantly increased in HepG2 cells expressing HBx (HepG2-HBx) and in non-tumor liver tissues of hepatitis B virus patients with high levels of HBx expression. In the liver of HBxTg mice, the expressions of gluconeogenic genes were also elevated, leading to hyperglycemia by increasing hepatic glucose production. However, this effect was insufficient to cause systemic insulin resistance. Importantly, the actions of HBx on hepatic glucose metabolism are thought to be mediated via iNOS signaling, as evidenced by the fact that deficiency of iNOS restored HBx-induced hyperglycemia by suppressing the gene expression of gluconeogenic enzymes. Treatment of HepG2-HBx cells with nitric oxide (NO) caused a significant increase in the expression of gluconeogenic genes, but JNK1 inhibition was completely normalized. Furthermore, hyperactivation of JNK1 in the liver of HBxTg mice was also suppressed in the absence of iNOS, indicating the critical role for JNK in the mutual regulation of HBx- and iNOS-mediated glucose metabolism. These findings establish a novel mechanism of HBx-driven hepatic metabolic disorder that is modulated by iNOS-mediated activation of JNK.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.