The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis
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, fr...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/7/1721 |
| _version_ | 1797538758934921216 |
|---|---|
| author | Arturo Simoni-Nieves Soraya Salas-Silva Lisette Chávez-Rodríguez Alejandro Escobedo-Calvario Matthis Desoteux Leticia Bucio Verónica Souza Roxana U. Miranda-Labra Linda E. Muñoz-Espinosa Cédric Coulouarn María Concepción Gutiérrez-Ruiz Jens U. Marquardt Luis E. Gomez-Quiroz |
| author_facet | Arturo Simoni-Nieves Soraya Salas-Silva Lisette Chávez-Rodríguez Alejandro Escobedo-Calvario Matthis Desoteux Leticia Bucio Verónica Souza Roxana U. Miranda-Labra Linda E. Muñoz-Espinosa Cédric Coulouarn María Concepción Gutiérrez-Ruiz Jens U. Marquardt Luis E. Gomez-Quiroz |
| author_sort | Arturo Simoni-Nieves |
| collection | DOAJ |
| description | 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 (<i>Slc41a; Fabp5; Igdcc4</i> and <i>Mthfd1l</i>) 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 |
| first_indexed | 2024-03-10T12:35:02Z |
| format | Article |
| id | doaj.art-a38051fc016d45d4ae8fc43eb1b7b82c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:35:02Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a38051fc016d45d4ae8fc43eb1b7b82c2023-11-21T14:19:17ZengMDPI AGCancers2072-66942021-04-01137172110.3390/cancers13071721The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor PrognosisArturo Simoni-Nieves0Soraya Salas-Silva1Lisette Chávez-Rodríguez2Alejandro Escobedo-Calvario3Matthis Desoteux4Leticia Bucio5Verónica Souza6Roxana U. Miranda-Labra7Linda E. Muñoz-Espinosa8Cédric Coulouarn9María Concepción Gutiérrez-Ruiz10Jens U. Marquardt11Luis E. Gomez-Quiroz12Posgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City 09340, MexicoPosgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City 09340, MexicoPosgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City 09340, MexicoPosgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City 09340, MexicoCentre de Lutte contre le Cancer Eugène Marquis, Inserm, Univ Rennes, COSS (Chemistry, Oncogenesis Stress Signaling), UMR_S 1242, 35042 Rennes, FranceÁrea de Medicina Experimental y Traslacional, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, MexicoÁrea de Medicina Experimental y Traslacional, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, MexicoÁrea de Medicina Experimental y Traslacional, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, MexicoLiver Unit, Department of Internal Medicine, “Dr. José E. González” University Hospital, Universidad Autónoma de Nuevo León, Monterrey 64460, NL, MexicoCentre de Lutte contre le Cancer Eugène Marquis, Inserm, Univ Rennes, COSS (Chemistry, Oncogenesis Stress Signaling), UMR_S 1242, 35042 Rennes, FranceÁrea de Medicina Experimental y Traslacional, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, MexicoDepartment of Medicine I, University Hospital Schleswig-Holstein, 23562 Lübeck, GermanyÁrea de Medicina Experimental y Traslacional, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, MexicoNon-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 (<i>Slc41a; Fabp5; Igdcc4</i> and <i>Mthfd1l</i>) 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 prognosishttps://www.mdpi.com/2072-6694/13/7/1721NAFLDNASHHCCcholesterolWestern diet |
| spellingShingle | Arturo Simoni-Nieves Soraya Salas-Silva Lisette Chávez-Rodríguez Alejandro Escobedo-Calvario Matthis Desoteux Leticia Bucio Verónica Souza Roxana U. Miranda-Labra Linda E. Muñoz-Espinosa Cédric Coulouarn María Concepción Gutiérrez-Ruiz Jens U. Marquardt Luis E. Gomez-Quiroz The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis Cancers NAFLD NASH HCC cholesterol Western diet |
| 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 | NAFLD NASH HCC cholesterol Western diet |
| url | https://www.mdpi.com/2072-6694/13/7/1721 |
| work_keys_str_mv | AT arturosimoninieves theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT sorayasalassilva theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT lisettechavezrodriguez theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT alejandroescobedocalvario theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT matthisdesoteux theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT leticiabucio theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT veronicasouza theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT roxanaumirandalabra theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT lindaemunozespinosa theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT cedriccoulouarn theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT mariaconcepciongutierrezruiz theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT jensumarquardt theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT luisegomezquiroz theconsumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT arturosimoninieves consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT sorayasalassilva consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT lisettechavezrodriguez consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT alejandroescobedocalvario consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT matthisdesoteux consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT leticiabucio consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT veronicasouza consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT roxanaumirandalabra consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT lindaemunozespinosa consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT cedriccoulouarn consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT mariaconcepciongutierrezruiz consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT jensumarquardt consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis AT luisegomezquiroz consumptionofcholesterolenricheddietsconditionsthedevelopmentofasubtypeofhccwithhighaggressivenessandpoorprognosis |