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The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis
SIMPLE SUMMARY: It is well known that non-alcoholic fatty liver disease is an important risk factor in the development of hepatocellular carcinoma, but the implication of cholesterol in this subject remains unclear, especially in western countries where its consumption is particularly elevated. This...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038696/ https://www.ncbi.nlm.nih.gov/pubmed/33917315 http://dx.doi.org/10.3390/cancers13071721 |
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author | Simoni-Nieves, Arturo Salas-Silva, Soraya Chávez-Rodríguez, Lisette Escobedo-Calvario, Alejandro Desoteux, Matthis Bucio, Leticia Souza, Verónica Miranda-Labra, Roxana U. Muñoz-Espinosa, Linda E. Coulouarn, Cédric Gutiérrez-Ruiz, María Concepción Marquardt, Jens U. Gomez-Quiroz, Luis E. |
author_facet | Simoni-Nieves, Arturo Salas-Silva, Soraya Chávez-Rodríguez, Lisette Escobedo-Calvario, Alejandro Desoteux, Matthis Bucio, Leticia Souza, Verónica Miranda-Labra, Roxana U. Muñoz-Espinosa, Linda E. Coulouarn, Cédric Gutiérrez-Ruiz, María Concepción Marquardt, Jens U. Gomez-Quiroz, Luis E. |
author_sort | Simoni-Nieves, Arturo |
collection | PubMed |
description | SIMPLE SUMMARY: It is well known that non-alcoholic fatty liver disease is an important risk factor in the development of hepatocellular carcinoma, but the implication of cholesterol in this subject remains unclear, especially in western countries where its consumption is particularly elevated. This work provides evidence of a cholesterol-related transcriptional fingerprint and its implications in the progression and aggressiveness of hepatocellular carcinoma with remarkable interest in clinical practice. ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) and progression to non-alcoholic steatohepatitis (NASH) result as a consequence of diverse conditions, mainly unbalanced diets. Particularly, high-fat and cholesterol content, as well as carbohydrates, such as those commonly ingested in Western countries, frequently drive adverse metabolic alterations in the liver and promote NAFLD development. Lipid liver overload is also one of the main risk factors for initiation and progression of hepatocellular carcinoma (HCC), but detailed knowledge on the relevance of high nutritional cholesterol remains elusive. We were aimed to characterize HCC development in mice fed with a Western diet (high in lipids and cholesterol) and to identify molecular alterations that define a subtype of liver cancer induced by lipid overload. Mice under western or high cholesterol diets more frequently developed tumors with a more aggressive phenotype than animals fed with a chow diet. Associated changes involved macrophage infiltration, angiogenesis, and stemness features. RNA-seq revealed a specific gene expression signature (Slc41a; Fabp5; Igdcc4 and Mthfd1l) resembling the adverse phenotypic features and poor clinical outcomes seen in patients with HCC. In conclusion; consumption of lipid enriched diets; particularly cholesterol; could accelerate HCC development with an aggressive phenotype and poor prognosis |
format | Online Article Text |
id | pubmed-8038696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80386962021-04-12 The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis Simoni-Nieves, Arturo Salas-Silva, Soraya Chávez-Rodríguez, Lisette Escobedo-Calvario, Alejandro Desoteux, Matthis Bucio, Leticia Souza, Verónica Miranda-Labra, Roxana U. Muñoz-Espinosa, Linda E. Coulouarn, Cédric Gutiérrez-Ruiz, María Concepción Marquardt, Jens U. Gomez-Quiroz, Luis E. Cancers (Basel) Article SIMPLE SUMMARY: It is well known that non-alcoholic fatty liver disease is an important risk factor in the development of hepatocellular carcinoma, but the implication of cholesterol in this subject remains unclear, especially in western countries where its consumption is particularly elevated. This work provides evidence of a cholesterol-related transcriptional fingerprint and its implications in the progression and aggressiveness of hepatocellular carcinoma with remarkable interest in clinical practice. ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) and progression to non-alcoholic steatohepatitis (NASH) result as a consequence of diverse conditions, mainly unbalanced diets. Particularly, high-fat and cholesterol content, as well as carbohydrates, such as those commonly ingested in Western countries, frequently drive adverse metabolic alterations in the liver and promote NAFLD development. Lipid liver overload is also one of the main risk factors for initiation and progression of hepatocellular carcinoma (HCC), but detailed knowledge on the relevance of high nutritional cholesterol remains elusive. We were aimed to characterize HCC development in mice fed with a Western diet (high in lipids and cholesterol) and to identify molecular alterations that define a subtype of liver cancer induced by lipid overload. Mice under western or high cholesterol diets more frequently developed tumors with a more aggressive phenotype than animals fed with a chow diet. Associated changes involved macrophage infiltration, angiogenesis, and stemness features. RNA-seq revealed a specific gene expression signature (Slc41a; Fabp5; Igdcc4 and Mthfd1l) resembling the adverse phenotypic features and poor clinical outcomes seen in patients with HCC. In conclusion; consumption of lipid enriched diets; particularly cholesterol; could accelerate HCC development with an aggressive phenotype and poor prognosis MDPI 2021-04-06 /pmc/articles/PMC8038696/ /pubmed/33917315 http://dx.doi.org/10.3390/cancers13071721 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Simoni-Nieves, Arturo Salas-Silva, Soraya Chávez-Rodríguez, Lisette Escobedo-Calvario, Alejandro Desoteux, Matthis Bucio, Leticia Souza, Verónica Miranda-Labra, Roxana U. Muñoz-Espinosa, Linda E. Coulouarn, Cédric Gutiérrez-Ruiz, María Concepción Marquardt, Jens U. Gomez-Quiroz, Luis E. The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis |
title | The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis |
title_full | The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis |
title_fullStr | The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis |
title_full_unstemmed | The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis |
title_short | The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis |
title_sort | consumption of cholesterol-enriched diets conditions the development of a subtype of hcc with high aggressiveness and poor prognosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038696/ https://www.ncbi.nlm.nih.gov/pubmed/33917315 http://dx.doi.org/10.3390/cancers13071721 |
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