The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis

Arturo Simoni-Nieves (1) , Soraya Salas-Silva (1) , Lisette Chavez-Rodriguez (1) , Alejandro Escobedo-Calvario (1) , Matthis Desoteux (2, 3) , Leticia Bucio (1) , Veronica Souza (1) , Roxana U. Miranda-Labra (1) , Linda E. Munoz-Espinosa (4) , Cédric Coulouarn (2, 3) , Maria Concepcion Gutierrez-Ruiz (1) , Jens U. Marquardt (5) , Luis E. Gomez-Quiroz (1)

1 UAM - Universidad Autonoma Metropolitana, Unidad Iztapalapa
2 COSS - Chemistry, Oncogenesis, Stress and Signaling
3 CRLCC - CRLCC Eugène Marquis
4 UANL - Universidad Autonoma de Nuevo Leon [Mexique]
5 UKSH - University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein

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 ( and ) 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.

Mots clés: NAFLD; NASH; HCC; cholesterol; Western diet

Domaines: Cancer

Arturo Simoni-Nieves, Soraya Salas-Silva, Lisette Chavez-Rodriguez, Alejandro Escobedo-Calvario, Matthis Desoteux, et al.. The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis. Cancers, 2021, 13 (7), ⟨10.3390/cancers13071721⟩. ⟨hal-03217238⟩