ArticlePloS one2014
HCC development is associated to peripheral insulin resistance in a mouse model of NASH.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 88 citations in OpenAlex.
- Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease.PloS one · 2018Trial
- Metabolic dysfunction‑associated steatotic liver disease: Pathogenesis, model and treatment (Review).International journal of molecular medicine · 2025Review
- Abnormalities of intracellular organelles in metabolic dysfunction-associated steatotic disease.Journal of gastroenterology · 2025Article
- Hepatocellular carcinoma in patients without cirrhosis.World journal of gastroenterology · 2025Review
- Review
- Progress in the Study of Animal Models of Metabolic Dysfunction-Associated Steatotic Liver Disease.Nutrients · 2024Review
- Preclinical Models of Hepatocellular Carcinoma: Current Utility, Limitations, and Challenges.Biomedicines · 2024Review
- Assessment of the Antioxidant and Hypolipidemic Properties ofAntioxidants (Basel, Switzerland) · 2024Article
- Review
- Serum resistin and the risk for hepatocellular carcinoma in diabetic patients.World journal of gastroenterology · 2023Review
- Article
- Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis.World journal of gastroenterology · 2023Review
- Article
- Obesity contributes to hepatocellular carcinoma development via immunosuppressive microenvironment remodeling.Frontiers in immunology · 2023Review
- Genetic and Diet-Induced Animal Models for Non-Alcoholic Fatty Liver Disease (NAFLD) Research.International journal of molecular sciences · 2022Review
- Mouse models of nonalcoholic steatohepatitis and their application to new drug development.Archives of pharmacal research · 2022Review
- Non-alcoholic fatty liver disease and hepatocellular carcinoma: Clinical challenges of an intriguing link.World journal of gastroenterology · 2022Review
- Antagonizing STK25 Signaling Suppresses the Development of Hepatocellular Carcinoma Through Targeting Metabolic, Inflammatory, and Pro-Oncogenic Pathways.Cellular and molecular gastroenterology and hepatology · 2022Article
- The Pathogenesis of HCC Driven by NASH and the Preventive and Therapeutic Effects of Natural Products.Frontiers in pharmacology · 2022Review
- Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: From Epidemiology to Diagnostic Approach.Cancers · 2021Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledNAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the absence of cirrhosis, that makes NAFLD of such clinical importance.
aimwe aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC.
methodsmice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control (CSAA diet) and subjected to a low-dose i.p. injection of CCl4 or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis.
resultsCDAA-treated mice showed peripheral insulin resistance at 1 month. At 1-3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+CCl4 treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors.
conclusionsthe CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD.
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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 Socratic graph.