Dataset Information

Characterizing the mechanism behind the progression of NAFLD to hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) developed in non-alcoholic fatty liver disease (NAFLD) individuals presents substantial clinical and biological characteristics, which remain to be elucidated. Its occurrence in noncirrhotic patients raises issues regarding surveillance strategies, which cannot be considered as cost-effective given the high prevalence of obesity and metabolic syndrome, and furthermore delineates specific oncogenic process that could be targeted in the setting of primary or secondary prevention. In this context, the identification of a genetic heterogeneity modulating HCC risk as well as specific biological pathways have been made possible through genome-wide association studies, development of animal models and in-depth analyses of human samples at the pathological and genomic levels. These advances must be confirmed and pursued to pave the way for personalized management of NAFLD-related HCC.

SUBMITTER: Nahon P

PROVIDER: S-EPMC7907968 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Characterizing the mechanism behind the progression of NAFLD to hepatocellular carcinoma.

Nahon Pierre P Allaire Manon M Nault Jean-Charles JC Paradis Valérie V

Hepatic oncology 20201229 4

Hepatocellular carcinoma (HCC) developed in non-alcoholic fatty liver disease (NAFLD) individuals presents substantial clinical and biological characteristics, which remain to be elucidated. Its occurrence in noncirrhotic patients raises issues regarding surveillance strategies, which cannot be considered as cost-effective given the high prevalence of obesity and metabolic syndrome, and furthermore delineates specific oncogenic process that could be targeted in the setting of primary or secondar ...[more]

PMID: 33680428

Similar Datasets

Project description:Background & aimsNon-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) is an increasing clinical problem associated with progression to hepatocellular carcinoma (HCC). The effect of a high-fat diet on the early immune response in HCC is poorly understood, while the role of metformin in treating NAFLD and HCC remains controversial. Herein, we visualized the early immune responses in the liver and the effect of metformin on progression of HCC using optically transparent zebrafish.MethodsWe used live imaging to visualize liver inflammation and disease progression in a NAFLD/NASH-HCC zebrafish model. We combined a high-fat diet with a transgenic zebrafish HCC model induced by hepatocyte-specific activated beta-catenin and assessed liver size, angiogenesis, micronuclei formation and inflammation in the liver. In addition, we probed the effects of metformin on immune cell composition and early HCC progression.ResultsWe found that a high-fat diet induced an increase in liver size, enhanced angiogenesis, micronuclei formation and neutrophil infiltration in the liver. Although macrophage number was not affected by diet, a high-fat diet induced changes in macrophage morphology and polarization with an increase in liver associated TNFα-positive macrophages. Treatment with metformin altered macrophage polarization, reduced liver size and reduced micronuclei formation in NAFLD/NASH-associated HCC larvae. Moreover, a high-fat diet reduced T cell density in the liver, which was reversed by treatment with metformin.ConclusionsThese findings suggest that diet alters macrophage polarization and exacerbates the liver inflammatory microenvironment and cancer progression in a zebrafish model of NAFLD/NASH-associated HCC. Metformin specifically affects the progression induced by diet and modulates the immune response by affecting macrophage polarization and T cell infiltration, suggesting possible effects of metformin on tumor surveillance.Lay summaryThis paper reports a new zebrafish model that can be used to study the effects of diet on liver cancer. We found that a high-fat diet promotes non-resolving inflammation in the liver and enhances cancer progression. In addition, we found that metformin, a drug used to treat diabetes, inhibits high-fat diet-induced cancer progression in this model, by reducing diet-induced non-resolving inflammation and potentially restoring tumor surveillance.

Dataset Information

Characterizing the mechanism behind the progression of NAFLD to hepatocellular carcinoma.

Publications

Characterizing the mechanism behind the progression of NAFLD to hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets