ArticleJHEP reports : innovation in hepatology2021
A human liver chimeric mouse model for non-alcoholic fatty liver disease.
Article in JHEP reports : innovation in hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- The Latest Therapeutic Targets and New Drug Research of Metabolic Dysfunction-Associated Steatotic Liver Disease.Clinical pharmacology and therapeutics · 2026Review
- Recent advances in the construction of humanized animal models and applications in translational medicine.Animal models and experimental medicine · 2026Review
- High-potency MyoAAV capsids enhanced skeletal muscle correction in a mouse model of GSD IIIa.Molecular therapy. Methods & clinical development · 2025Article
- Unlocking the lipid code: SREBPs as key drivers in gastrointestinal tumour metabolism.Lipids in health and disease · 2025Review
- A diet-driven metabolic dysfunction-associated steatohepatitis (MASH) mouse model resembles the corresponding human disease.Journal of molecular histology · 2025Article
- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Islet single-cell transcriptomic profiling during obesity-induced beta cell expansion in female mice.iScience · 2025Article
- Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): the interplay of gut microbiome, insulin resistance, and diabetes.Frontiers in medicine · 2025Review
- Mice Engrafted with Human Liver Cells.Seminars in liver disease · 2024Review
- A sexually dimorphic hepatic cycle of periportal VLDL generation and subsequent pericentral VLDLR-mediated re-uptake.Nature communications · 2024Article
- The impact of steatotic liver disease on coronary artery disease through changes in the plasma lipidome.Scientific reports · 2024Article
- A novel hepatocyte ketone production assay to help the selection of nutrients for the ketogenic diet treatment of epilepsy.Scientific reports · 2024Article
- Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered metabolism, cell senescence, and nonalcoholic fatty liver disease.Science advances · 2024Article
- An effective MASH drug is good, but biotech can make it better.Nature biotechnology · 2024Article
- Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress.Epigenetics & chromatin · 2024Article
- A humanized mouse model for adeno-associated viral gene therapy.Nature communications · 2024Article
- Circadian dysfunction induces NAFLD-related human liver cancer in a mouse model.Journal of hepatology · 2024Article
- Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress.bioRxiv : the preprint server for biology · 2024Article
- Spatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2024Article
- Antifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach.Nature reviews. Gastroenterology & hepatology · 2023Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe accumulation of neutral lipids within hepatocytes underlies non-alcoholic fatty liver disease (NAFLD), which affects a quarter of the world's population and is associated with hepatitis, cirrhosis, and hepatocellular carcinoma. Despite insights gained from both human and animal studies, our understanding of NAFLD pathogenesis remains limited. To better study the molecular changes driving the condition we aimed to generate a humanised NAFLD mouse model.
methodsWe generated TIRF (transgene-free
resultsWithin the same chimeric liver, human hepatocytes developed pronounced steatosis whereas murine hepatocytes remained normal. Unbiased metabolomics and lipidomics revealed signatures of clinical NAFLD. Transcriptomic analyses showed that molecular responses diverged sharply between murine and human hepatocytes, demonstrating stark species differences in liver function. Regulatory network analysis indicated close agreement between our model and clinical NAFLD with respect to transcriptional control of cholesterol biosynthesis.
conclusionsThese NAFLD xenograft mice reveal an unexpected degree of evolutionary divergence in food metabolism and offer a physiologically relevant, experimentally tractable model for studying the pathogenic changes invoked by steatosis. LAY SUMMARY: Fatty liver disease is an emerging health problem, and as there are no good experimental animal models, our understanding of the condition is poor. We here describe a novel humanised mouse system and compare it with clinical data. The results reveal that the human cells in the mouse liver develop fatty liver disease upon a Western-style fatty diet, whereas the mouse cells appear normal. The molecular signature (expression profiles) of the human cells are distinct from the mouse cells and metabolic analysis of the humanised livers mimic the ones observed in humans with fatty liver. This novel humanised mouse system can be used to study human fatty liver disease.
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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.